Tokushima University / Educator and Researcher Directory --- Ishimaru, Naozumi

Personal Web Page

https://researchmap.jp/read0191790 (researchmap)

https://orcid.org/0000-0003-1087-8338 (ORCID)

Field of Study

○	Pathology, Immunology

Subject of Study

○	Molecular mechanism of autoimmune diseases (autoimmune, T cell activation, NF-kB, sex hormone, Sjögren's syndrome)

Book / Paper

Book:

1.	Kunihiro Otsuka, Takaaki Tsunematsu and Naozumi Ishimaru : シェーグレン症候群の病理診断, 日本病理学会,
2.	Takaaki Tsunematsu, 俵宏彰, Kunihiro Otsuka, Aya Ushio and Naozumi Ishimaru : ヒトパピローマウイルス陽性がんにおける脱ユビキチン化酵素の役割, 日本口腔組織培養学会, Nov. 2022.
3.	Kunihiro Otsuka, Takaaki Tsunematsu, Aya Ushio, Mami Sato and Naozumi Ishimaru : シェーグレン症候群の病理, Oct. 2022.
4.	恒吉正澄, 小田義直, 相島慎一 and Naozumi Ishimaru : わかりやすい病理学改訂第7版, Mar. 2021.
5.	Naozumi Ishimaru : 生体の科学, Mar. 2020.
6.	Yosuke Shikama, Naozumi Ishimaru, Yasusei Kudo, Rieko Arakaki, Yukiko Bandou, Nanako Aki and Makoto Funaki : High Levels of Saturated Fatty Acids may Exacerbate the Pathogenesis of Primary Sjögrens Syndrome, Springer, Dec. 2014.
7.	Yoshio Hayashi and Naozumi Ishimaru : Handbook on Immunosenescence, Springer Japan, Apr. 2009.
8.	Yoshio Hayashi and Naozumi Ishimaru : 口唇腺生検病理診断「シェーグレン症候群の診断と治療マニュアル」, 株式会社診断と治療社, Tokyo, Apr. 2009.
9.	Yoshio Hayashi and Naozumi Ishimaru : Autoimmunity-Aging Mouse Model for Autoimmune Diseases, Jan. 2009.
10.	Naozumi Ishimaru, 岸本英博 and Yoshio Hayashi : T細胞レセプターシグナルとNF-κB, 2007.

Academic Paper (Judged Full Paper):

1.	Daishiro Kobayashi, Masaya Denda, Junya Hayashi, Kohta Hidaka, Yutaka Kohmura, Takaaki Tsunematsu, Kohei Nishino, Harunori Yoshikawa, OHKAWACHI Kento, Kiyomi Nigorikawa, Tetsuro Yoshimaru, Naozumi Ishimaru, Wataru Nomura, Toyomasa Katagiri, Hidetaka Kosako and Akira Otaka : Sulfoxide-Mediated Cys-Trp-Selective Bioconjugation that Enables Protein Labeling and Peptide Heterodimerization, ChemistryEurope, Vol.2, No.3-4, 2024. (Link to Publication Site) ● Publication site (DOI): 10.1002/ceur.202400014 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1002/ceur.202400014 (DOI: 10.1002/ceur.202400014)
2.	Keiko Aota, Kohichi Kani, Shinji Ono, Kohei Naniwa, Yukihiro Momota, Makoto Fukui, Naozumi Ishimaru and Masayuki Azuma : Activation of Janus kinase 2 contributes to the autoimmune pathology in the salivary glands of patients with Sjögren's syndrome, Oral Science International, 2024. (Tokushima University Institutional Repository) ● Metadata: 119316 (Link to Publication Site) ● Publication site (DOI): 10.1002/osi2.1241 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1002/osi2.1241 (Tokushima University Institutional Repository: 119316, DOI: 10.1002/osi2.1241)
3.	Hiroaki Tawara, Takaaki Tsunematsu, Ruka Nagao, Shigefumi Matsuzawa, Kunihiro Otsuka, Aya Ushio and Naozumi Ishimaru : The noncanonical function of borealin, a component of chromosome passenger complex, promotes glycolysis via stabilization of survivin in squamous cell carcinoma cells., Biochemical and Biophysical Research Communications, Vol.706, 149741, 2024. (Summary) The chromosome passenger complex (CPC) is a kinase complex formed by Aurora B, borealin, survivin and inner centromere protein (INCENP). The CPC is active during mitosis and contributes to proper chromosome segregation via the phosphorylation of various substrates. Overexpression of each CPC component has been reported in most cancers. However, its significance remains unclear, as only survivin is known to confer chemoresistance. This study showed that the overexpression of borealin, a CPC component, stabilized survivin protein depending on its interaction with survivin. Unexpectedly, the accumulation of survivin by borealin overexpression did not affect the well-characterized functions of survivin, such as chemoresistance and cell proliferation. Interestingly, the overexpression of borealin promoted lactate production but not the overexpression of the deletion mutant that lacks the ability to bind to survivin. Consistent with these findings, the expression levels of glycolysis-related genes were enhanced in borealin-overexpressing cancer cells. Meanwhile, the overexpression of survivin alone did not promote lactate production. Overall, the accumulation of the borealin-survivin complex promoted glycolysis in squamous cell carcinoma cells. This mechanism may contribute to cancer progression via excessive lactate production. (Keyword) Humans / Survivin / Centromere / Chromosomal Proteins, Non-Histone / Cell Cycle Proteins / Mitosis / Phosphorylation / Aurora Kinase B / Carcinoma, Squamous Cell / Lactates (Tokushima University Institutional Repository) ● Metadata: 119377 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2024.149741 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38471204 ● Search Scopus @ Elsevier (PMID): 38471204 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2024.149741 (Tokushima University Institutional Repository: 119377, DOI: 10.1016/j.bbrc.2024.149741, PubMed: 38471204)
4.	Shengjian Jin, Takaaki Tsunematsu, Taigo Horiguchi, Yasuhiro Mouri, Wenhua Shao, Keiko Miyoshi, Hiroko Hagita, Motoharu Sarubo, Natsumi Fujiwara, Qi Guangying, Naozumi Ishimaru and Yasusei Kudo : Involvement of the OTUB1-YAP1 axis in driving malignant behaviors of head and neck squamous cell carcinoma., Cancer Medicine, Vol.12, No.24, 22156-22169, 2023. (Summary) This study highlights the critical role of OTUB1 in HNSCC progression via modulating YAP1. Targeting the OTUB1-YAP1 axis holds promise as a potential therapeutic strategy for HNSCC treatment. (Keyword) deubiquitinating enzyme (DUB) / head and neck squamous cell carcinoma / invasion / OTUB1 / YAP (Tokushima University Institutional Repository) ● Metadata: 118778 (Link to Publication Site) ● Publication site (DOI): 10.1002/cam4.6735 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37986681 ● CiNii @ National Institute of Informatics (CRID): 1940583859514191616 ● Summary page in Scopus @ Elsevier: 2-s2.0-85177448617 (Tokushima University Institutional Repository: 118778, DOI: 10.1002/cam4.6735, PubMed: 37986681, CiNii: 1940583859514191616, Elsevier: Scopus)
5.	富田満, Hirohisa Ogawa, Takaaki Tsunematsu, Mami Sato, 山下貴央, Yoshiaki Kitamura, Naozumi Ishimaru, Koichi Tsuneyama, Hisanori Uehara and Yoshimi Bando : 線維化と腫瘍随伴リンパ組織増生を伴う粘表皮癌の1例, 診断病理, Vol.40, No.4, 336-341, 2023.
6.	Mami Sato-Fukuba, Rieko Arakaki, Aya Ushio, Kunihiro Otsuka, Ruka Nagao, Shigefumi Matsuzawa, Hiroaki Tawara, Takaaki Tsunematsu and Naozumi Ishimaru : CD4 T-cell-dependent differentiation of CD23 follicular B cells contributes to the pulmonary pathology in a primary Sjögren's syndrome mouse model., Frontiers in Immunology, Vol.14, 1217492, 2023. (Summary) Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that affects the function of exocrine glands, such as the lacrimal and the salivary glands. Extraglandular lesions and malignant lymphoma also occur during the progressive stage of pSS. We have, herein, focused on the pulmonary lesions of pSS and have aimed clarifying their pathophysiological mechanism by comparing the glandular with the extraglandular lesions observed in a mouse model of pSS. The histopathological analysis of lung tissues obtained from NFS/ mice that have undergone neonatal thymectomy was performed. Moreover, and experiments were conducted along with immunological analyses in order to characterize the unique phenotypes of the pulmonary lesions identified in these pSS model mice. Inflammatory lesions with a bronchus-associated lymphoid tissue-like structure were identified in the lungs of pSS model mice. In addition, relative to salivary gland lesions, pulmonary lesions showed increased CD23 follicular B (FB) cells. and pulmonary B cells were more readily driven to CD23 FB cell phenotype than salivary gland B cells in pSS model mice. Furthermore, the CD23 FB cell differentiation was found to be enhanced in a CD4 T-cell-dependent manner under a Th2-type condition in the lungs of herein examined pSS model mice. A Th2-type response in the pSS lung may promote the progression of autoimmune lesions through an enhanced abnormal differentiation of B cells. (Keyword) Mice / Animals / Sjögren's syndrome / salivary glands / B-Lymphocytes / cell differentiation / CD4-Positive T-Lymphocytes (Tokushima University Institutional Repository) ● Metadata: 118467 (Link to Publication Site) ● Publication site (DOI): 10.3389/fimmu.2023.1217492 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37475871 ● Summary page in Scopus @ Elsevier: 2-s2.0-85165185874 (Tokushima University Institutional Repository: 118467, DOI: 10.3389/fimmu.2023.1217492, PubMed: 37475871, Elsevier: Scopus)
7.	Anrizandy Narwidina, Aya Miyazaki, Kokoro Iwata, Rika Kurogoushi, Asuna Sugimoto, Yasusei Kudo, Keita Kawarabayashi, Yoshihito Yamakawa, Yuki Akazawa, Takamasa Kitamura, Hiroshi Nakagawa, Kimiko Ueda Yamaguchi, Tomokazu Hasegawa, Keigo Yoshizaki, Satoshi Fukumoto, Akihito Yamamoto, Naozumi Ishimaru, Tomonori Iwasaki and Tsutomu Iwamoto : Iroquois homeobox 3 regulates odontoblast proliferation and differentiation mediated by Wnt5a expression., Biochemical and Biophysical Research Communications, Vol.650, 47-54, 2023. (Summary) Iroquois homeobox (Irx) genes are TALE-class homeobox genes that are evolutionarily conserved across species and have multiple critical cellular functions in fundamental tissue development processes. Previous studies have shown that Irxs genes are expressed during tooth development. However, the precise roles of genes in teeth remain unclear. Here, we demonstrated for the first time that Irx3 is an essential molecule for the proliferation and differentiation of odontoblasts. Using cDNA synthesized from postnatal day 1 (P1) tooth germs, we examined the expression of all Irx genes (Irx1-Irx6) by RT-PCR and found that all genes except Irx4 were expressed in the tooth tissue. Irx1-Irx3 a were expressed in the dental epithelial cell line M3H1 cells, while Irx3 and Irx5 were expressed in the dental mesenchymal cell line mDP cells. Only Irx3 was expressed in both undifferentiated cell lines. Immunostaining also revealed the presence of IRX3 in the dental epithelial cells and mesenchymal condensation. Inhibition of endogenous Irx3 by siRNA blocks the proliferation and differentiation of mDP cells. Wnt3a, Wnt5a, and Bmp4 are factors involved in odontoblast differentiation and were highly expressed in mDP cells by quantitative PCR analysis. Interestingly, the expression of Wnt5a (but not Wnt3a or Bmp4) was suppressed by Irx3 siRNA. These results suggest that Irx3 plays an essential role in part through the regulation of Wnt5a expression during odontoblast proliferation and differentiation. (Keyword) Homeodomain Proteins / Transcription Factors / Odontoblasts / Genes, Homeobox / cell differentiation / cell proliferation and differentiation (Tokushima University Institutional Repository) ● Metadata: 118052 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2023.02.004 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36773339 ● Search Scopus @ Elsevier (PMID): 36773339 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2023.02.004 (Tokushima University Institutional Repository: 118052, DOI: 10.1016/j.bbrc.2023.02.004, PubMed: 36773339)
8.	Wenhua Shao, Takaaki Tsunematsu, Masaaki Umeda, Hiroaki Tawara, Natsumi Fujiwara, Yasuhiro Mouri, Rieko Arakaki, Naozumi Ishimaru and Yasusei Kudo : Cancer cell-derived novel periostin isoform promotes invasion in head and neck squamous cell carcinoma., Cancer Medicine, Vol.12, No.7, 8510-8525, 2023. (Summary) It recently has been reported that partial-epithelial-mesenchymal transition (p-EMT) program is associated with metastasis in head and neck squamous cell carcinoma (HNSCC). We previously have identified POSTN (which encodes periostin) as an invasion-promoting molecule in HNSCC. Interestingly, POSTN expression is frequently observed in cancer cells with higher p-EMT score by using a previous single-cell transcriptomic data of HNSCC cases. Although it is known that POSTN has 11 splicing variants, the role of them has not been determined in HNSCC. Here, we found that HNSCC cells with EMT features expressed POSTN isoforms, Iso3 (lacking exon 17 and 21) and Iso5 (lacking exon 17), whereas fibroblast expressed Iso3 and Iso4 (lacking exon 17, 18, and 21). The expression of POSTN Iso3 and Iso4 are known to be widely observed in various cell types including stromal cells. Therefore, we focused on the role of novel cancer cell-derived POSTN isoform, Iso5, in HNSCC. Single overexpression of POSTN Iso5 as well as Iso3 promoted invasion. Surprisingly, Iso5 synergistically promoted invasion together with Iso3. Notably, Iso5 as well as Iso3 upregulated p-EMT-related genes. We suggest that a novel cancer-specific POSTN isoform lacking exon 17 (Iso5) can be a useful marker for detecting cancer cells undergoing p-EMT. Moreover, a POSTN Iso5 can be a novel target for diagnosis and therapy in HNSCC. (Tokushima University Institutional Repository) ● Metadata: 118312 (Link to Publication Site) ● Publication site (DOI): 10.1002/cam4.5601 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36691359 ● Search Scopus @ Elsevier (PMID): 36691359 ● Search Scopus @ Elsevier (DOI): 10.1002/cam4.5601 (Tokushima University Institutional Repository: 118312, DOI: 10.1002/cam4.5601, PubMed: 36691359)
9.	Mami Sato, Rieko Arakaki, Hiroaki Tawara, Ruka Nagao, Hidetaka Tanaka, Kai Tamura, Yuki Kawahito, Aya Ushio, Takaaki Tsunematsu and Naozumi Ishimaru : Disturbed natural killer cell homeostasis in the salivary gland enhances autoimmune pathology via IFN-γ in a mouse model of primary Sjogren's syndrome., Frontiers in Medicine, Vol.9, 1036787, 2022. (Summary) Innate lymphoid cells (ILCs), including natural killer (NK) cells, ILC1, ILC2, lymphoid tissue-inducer (LTi) cells, and ILC3 cell, play a key role in various immune responses. Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by chronic inflammation of exocrine glands, such as the lacrimal and salivary glands (SGs). The role of NK cells among ILCs in the pathogenesis of pSS is still unclear. In this study, the characteristics and subsets of NK cells in the salivary gland (SG) tissue were analyzed using a murine model of pSS. Multiple phenotypes and cytotoxic signature of the SG NK cells in control and pSS model mice were evaluated by flow cytometric analysis. Intracellular expression of interferon-γ (IFN-γ) among T cells and NK cells from the SG tissues was compared by experiments. In addition, pathological analysis was performed using anti-asialo-GM1 (ASGM1) antibody (Ab)-injected pSS model mice. The number of conventional NK (cNK) cells in the SG of pSS model mice significantly increased compared with that in control mice at 6 weeks of age. The production level of IFN-γ was significantly higher in SG NK cells than in SG T cells. The depletion of NK cells by ASGM1 Ab altered the ratio of tissue resident NK (rNK) cells to cNK cells, which inhibited the injury to SG cells with the recovery of saliva secretion in pSS model mice. The results indicate that SG cNK cells may enhance the autoreactive response in the target organ by upregulating of IFN-γ, whereas SG rNK cells protect target cells against T cell cytotoxicity. Therefore, the activation process and multiple functions of NK cells in the target organ could be helpful to develop potential markers for determining autoimmune disease activity and target molecules for incurable immune disorders. (Tokushima University Institutional Repository) ● Metadata: 118305 (Link to Publication Site) ● Publication site (DOI): 10.3389/fmed.2022.1036787 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36388880 ● Search Scopus @ Elsevier (PMID): 36388880 ● Search Scopus @ Elsevier (DOI): 10.3389/fmed.2022.1036787 (Tokushima University Institutional Repository: 118305, DOI: 10.3389/fmed.2022.1036787, PubMed: 36388880)
10.	Ryosuke Nagatomo, Haruki Kaneko, Shihori Kamatsuki, Mayuko Shimizu, Naozumi Ishimaru, Koichi Tsuneyama and Koichi Inoue : Short-chain fatty acid profiling in biological samples from a mouse model of Sjögrens syndrome based on derivatized LC-MS/MS assay., Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, Vol.1210, 123432, 2022. (Summary) An analytical platform is required to characterize the short-chain fatty acids (SCFAs) in a mouse model of pathological immune conditions. Therefore, liquid chromatography tandem mass spectrometry combined with 2-picolylamine derivatization and a comprehensive study of SCFAs distribution based on serum, saliva, feces, liver, and brain from a mouse model of Sjögren's syndrome (SS) is performed. The design of experiments is used to achieve efficient 2-picolylamine derivatization, and optimize the reaction conditions. Twelve SCFAs are derivatized, and separated on a reversed-phase C column. All SCFAs show high linearity (r > 0.995) and intra/inter-day accuracy values from 71.6% to 115.6% (precision < 13.7%). This method was used to determine SCFAs concentrations in the serum, saliva, feces, liver, and brain of an SS model mice, and isobutyric acid, valeric acid, isovaleric acid, and 2-methylbutyric acid in liver from SS were significantly different compared with control group. Moreover, the preliminary evaluation of propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid in saliva is conducted based on the respective SS stages and are correlated with these histological scores. This analytical platform for the widely SCFAs profiling in several tissues can be a clue for studying unclear immune pathophysiology. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.jchromb.2022.123432 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36063699 ● Summary page in Scopus @ Elsevier: 2-s2.0-85137093675 (DOI: 10.1016/j.jchromb.2022.123432, PubMed: 36063699, Elsevier: Scopus)
11.	Takaaki Tsunematsu, Rieko Arakaki, Mami Sato, Masako Saito, Kunihiro Otsuka, Furukawa Yusuke, Taquahashi Yuhji, Kanno Jun and Naozumi Ishimaru : Exposure to Multiwall Carbon Nanotubes Promotes Fibrous Proliferation by Production of Matrix Metalloproteinase-12 via NF-κB Activation in Chronic Peritonitis., The American Journal of Pathology, Vol.S0002-9440, No.22, 00240, 2022. (Summary) The toxicologic effects of nanomaterials, such as carbon nanotubes (CNTs), on the immune system are considerably understood. However, the precise relationship between long-term exposure to CNTs and chronic inflammation remains unclear. In this study, a mouse model of chronic peritonitis was established using i.p. injection of multiwalled CNTs treated by the Taquann method with high dispersion efficiency. Chronic peritonitis with fibrosis was observed in Taquann-treated multiwalled CNT (T-CNT)-injected mice, but not in Taquann-treated titanium dioxide-injected mice. In vivo and in vitro experiments showed that matrix metalloproteinase-12 (MMP-12) of macrophages was up-regulated by T-CNT to enhance fibroblast activation and profibrotic molecule expression in fibroblasts. In addition, T-CNT-induced peritonitis reduced MMP-12 expression in Nfκb1 mice, suggesting that MMP-12-producing macrophages play a key role in chronic inflammation due to T-CNT exposure through NF-κB activation. The results of this study could be helpful in understanding the molecular toxicity of nanomaterial and chronic inflammation. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ajpath.2022.07.009 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35963465 ● Search Scopus @ Elsevier (PMID): 35963465 ● Search Scopus @ Elsevier (DOI): 10.1016/j.ajpath.2022.07.009 (DOI: 10.1016/j.ajpath.2022.07.009, PubMed: 35963465)
12.	Yuto Horii, Toshiki Iniwa, Masayoshi Onitsuka, Jun Tsukimoto, Yuki Tanaka, Hironobu Ike, Yuri Fukushi, Haruna Andoh, Yoshie Takeuchi, So-ichiro Nishioka, Daisuke Tsuji, Mariko Ikuo, Naoshi Yamazaki, Yoshiharu Takiguchi, Naozumi Ishimaru and Kouji Itou : Reversal of neuroinflammation in novel galactosialidosis model mice by single intracerebroventricular administration of CHO-derived human recombinant cathepsin A precursor protein., Molecular Therapy. Methods & Clinical Development, Vol.25, No.June, 297-310, 2022. (Tokushima University Institutional Repository) ● Metadata: 117739 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.omtm.2022.04.001 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1016/j.omtm.2022.04.001 (Tokushima University Institutional Repository: 117739, DOI: 10.1016/j.omtm.2022.04.001)
13.	Kunihiro Otsuka, Mami Sato, Takaaki Tsunematsu and Naozumi Ishimaru : Virus Infections Play Crucial Roles in the Pathogenesis of Sjögren's Syndrome., Viruses, Vol.14, No.7, 1474, 2022. (Summary) Sjögren's syndrome (SS) is an autoimmune disease especially targeting exocrine glands, such as the salivary and lacrimal glands. A radical therapy for SS based on its etiology has not been established because of the complex pathogenesis of the disease. Several studies have demonstrated a relationship between virus infection and SS pathogenesis. In particular, infection with the Epstein-Barr (EB) virus among others is a potent factor associated with the onset or development of SS. Specifically, virus infection in the target organs of SS triggers or promotes autoreactive responses involving the process of autoantigen formation, antigen-presenting function, or T-cell response. Our review of recent research highlights the crucial roles of virus infection in the pathogenesis of SS and discusses the critical association between virus infection and the etiology of autoimmunity in SS. (Keyword) Autoantigens / autoimmunity / Herpesvirus 4, Human / Humans / Sjögren's syndrome / Virus Diseases (Tokushima University Institutional Repository) ● Metadata: 117727 (Link to Publication Site) ● Publication site (DOI): 10.3390/v14071474 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35891453 ● Summary page in Scopus @ Elsevier: 2-s2.0-85133687255 (Tokushima University Institutional Repository: 117727, DOI: 10.3390/v14071474, PubMed: 35891453, Elsevier: Scopus)
14.	Takumi Maruhashi, Daisuke Sugiura, Il-mi Okazaki, Kenji Shimizu, K Takeo Maeda, Jun Ikubo, Harunori Yoshikawa, Katsumi Maenaka, Naozumi Ishimaru, Hidetaka Kosako, Tatsuya Takemoto and Taku Okazaki : Binding of LAG-3 to stable peptide-MHC class II limits T cell function and suppresses autoimmunity and anti-cancer immunity., Immunity, Vol.55, No.5, 912-924.e8, 2022. (Summary) Lymphocyte activation gene-3 (LAG-3) is a potent inhibitory co-receptor; yet, its functional ligand remains elusive, with distinct potential ligands identified. Here, we investigated the relative contribution of potential ligands, stable peptide-MHC class II complexes (pMHCII) and fibrinogen-like protein 1 (FGL1), to LAG-3 activity invitro and invivo. Binding of LAG-3 to stable pMHCII but not to FGL1 induced Tcell suppression invitro. Consistently, LAG-3 mutants lacking FGL1-binding capacity but not those lacking stable pMHCII-binding capacity retained suppressive activity invitro. Accordingly, targeted disruption of stable pMHCII- but not FGL1-binding capacity of LAG-3 in NOD mice recapitulated diabetes exacerbation by LAG-3 deficiency. Additionally, the loss of stable pMHCII-binding capacity of LAG-3 augmented anti-cancer immunity comparably with LAG-3 deficiency in C57BL/6 mice. These results identify stable pMHCII as a functional ligand of LAG-3 both in autoimmunity and anti-cancer immunity. Thus, stable pMHCII-LAG-3 interaction is a potential therapeutic target in human diseases. (Keyword) Animals / Antigens, CD / Autoimmunity / Histocompatibility Antigens Class II / Ligands / Mice / Mice, Inbred C57BL / Mice, Inbred NOD / Neoplasms / Peptides / T-Lymphocytes (Link to Publication Site) ● Publication site (DOI): 10.1016/j.immuni.2022.03.013 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35413245 ● Search Scopus @ Elsevier (PMID): 35413245 ● Search Scopus @ Elsevier (DOI): 10.1016/j.immuni.2022.03.013 (DOI: 10.1016/j.immuni.2022.03.013, PubMed: 35413245)
15.	Yosuke Shikama, Mie Kurosawa, Masae Furukawa, Yasusei Kudo, Naozumi Ishimaru and Kenji Matsushita : The Priming Potential of Interferon Lambda-1 for Antiviral Defense in the Oral Mucosa., Inflammation, Vol.45, No.3, 1348-1361, 2022. (Summary) The oral mucosa is one of the first lines of the innate host defense system against microbial invasion. Interferon (IFN) lambda-1 (IFN-λ1), a type III IFN, exhibits type I IFN-like antiviral activity. In contrast to ubiquitously expressed type I IFN receptors, IFN-λ receptor 1 (IFN-λR1), which has higher affinity for type III IFNs than low-affinity interleukin (IL)-10 receptor 2, is mainly expressed on epithelial cells. Although IFN-λ1 has been shown to exert antiviral effects in the respiratory tract, gastrointestinal tract, and skin, the regulation of type III IFN receptor expression and its functions in the oral mucosa remain unclear. We herein showed the expression of IFN-λR1 in human gingival keratinocytes. The expression of IL-6, angiotensin-converting enzyme 2 (a critical molecule for severe acute respiratory syndrome coronavirus 2 infection), and IL-8 in human primary gingival keratinocytes (HGK) were significantly higher following treatments with either type I IFN (IFN-β) or type II IFN (IFN-γ) than with IFN-λ1. However, the IFN-λ1 treatment strongly induced toll-like receptor (TLR) 3 and retinoic acid-inducible gene I (RIG-I), which mainly recognize viral nucleic acids, via the STAT1-mediated pathway. Furthermore, a stimulation with a RIG-I or TLR3 agonist promoted the production of IL-6, IL-8, and IFN-λ in HGK, which was significantly enhanced by a pretreatment with IFN-λ1. These results suggest that IFN-λ1 may contribute to the activation of innate immune responses to oral viral infections by up-regulating the expression of RIG-I and TLR3 and priming their functions in keratinocytes. (Keyword) Antiviral Restriction Factors / DEAD Box Protein 58 / Humans / Immunity, Innate / Interferons / Interleukin-6 / Interleukin-8 / Mouth Mucosa / Receptors, Immunologic / Toll-Like Receptor 3 (Link to Publication Site) ● Publication site (DOI): 10.1007/s10753-022-01624-1 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35044570 ● Search Scopus @ Elsevier (PMID): 35044570 ● Search Scopus @ Elsevier (DOI): 10.1007/s10753-022-01624-1 (DOI: 10.1007/s10753-022-01624-1, PubMed: 35044570)
16.	Kokoro Iwata, Keita Kawarabayashi, Keigo Yoshizaki, Tian Tian, Kan Saito, Asuna Sugimoto, Rika Kurogoushi, Aya Yamada, Akihito Yamamoto, Yasusei Kudo, Naozumi Ishimaru, Satoshi Fukumoto and Tsutomu Iwamoto : von Willebrand factor D and EGF domains regulate ameloblast differentiation and enamel formation., Journal of Cellular Physiology, Vol.237, No.3, 1964-1979, 2021. (Summary) Cell- and tissue-specific extracellular matrix (ECM) composition plays an important role in organ development, including teeth, by regulating cell behaviors, such as cell proliferation and differentiation. Here, we demonstrate for the first time that von Willebrand factor D and epidermal growth factor (EGF) domains (Vwde), a previously uncharacterized ECM protein, is specifically expressed in teeth and regulates cell proliferation and differentiation in inner enamel epithelial cells (IEEs) and enamel formation. We identified the Vwde as a novel ECM protein through bioinformatics using the NCBI expressed sequence tag database for mice. Vwde complementary DNA encodes 1773 amino acids containing a signal peptide, a von Willebrand factor type D domain, and tandem calcium-binding EGF-like domains. Real-time polymerase chain reaction demonstrated that Vwde is highly expressed in tooth tissue but not in other tissues including the brain, lung, heart, liver, kidney, and bone. In situ hybridization revealed that the IEEs expressed Vwde messenger RNA in developing teeth. Immunostaining showed that VWDE was localized at the proximal and the distal ends of the pericellular regions of the IEEs. Vwde was induced during the differentiation of mouse dental epithelium-derived M3H1 cells. Vwde-transfected M3H1 cells secreted VWDE protein into the culture medium and inhibited cell proliferation, whereas ameloblastic differentiation was promoted. Furthermore, Vwde increased the phosphorylation of extracellular signal-regulated kinase 1/2 and protein kinase B and strongly induced the expression of the intercellular junction protein, N-cadherin (Ncad). Interestingly, the suppression of endogenous Vwde inhibited the expression of Ncad. Finally, we created Vwde-knockout mice using the CRISPR-Cas9 system. Vwde-null mice showed low mineral density, rough surface, and cracks in the enamel, indicating the enamel hypoplasia phenotype. Our findings suggest that Vwde assembling the matrix underneath the IEEs is essential for Ncad expression and enamel formation. (Link to Publication Site) ● Publication site (DOI): 10.1002/jcp.30667 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34957547 ● Search Scopus @ Elsevier (PMID): 34957547 ● Search Scopus @ Elsevier (DOI): 10.1002/jcp.30667 (DOI: 10.1002/jcp.30667, PubMed: 34957547)
17.	Shu Chen, Naofumi Tamaki, Yasusei Kudo, Takaaki Tsunematsu, Kaname Miki, Naozumi Ishimaru and Hiro-O Ito : Protective effects of resveratrol against 5-fluorouracil-induced oxidative stress and inflammatory responses in human keratinocytes., Journal of Clinical Biochemistry and Nutrition, Vol.69, No.3, 238-246, 2021. (Summary) -acetylcysteine reduced ROS levels without affecting the expression of pro-inflammatory cytokines. Resveratrol might be useful for preventing 5-FU-induced adverse effects by activating anti-oxidant and anti-inflammatory responses. (Tokushima University Institutional Repository) ● Metadata: 116380 (Link to Publication Site) ● Publication site (DOI): 10.3164/jcbn.21-23 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34857985 ● Search Scopus @ Elsevier (PMID): 34857985 ● Search Scopus @ Elsevier (DOI): 10.3164/jcbn.21-23 (Tokushima University Institutional Repository: 116380, DOI: 10.3164/jcbn.21-23, PubMed: 34857985)
18.	Wenhua Shao, Natsumi Fujiwara, Yasuhiro Mouri, Satoru Kisoda, Kayo Yoshida, Kaya Yoshida, Hiromichi Yumoto, Kazumi Ozaki, Naozumi Ishimaru and Yasusei Kudo : Conversion from epithelial to partial-EMT phenotype by Fusobacterium nucleatum infection promotes invasion of oral cancer cells., Scientific Reports, Vol.11, No.1, 14943, 2021. (Summary) The ability of cancer cells to undergo partial-epithelial mesenchymal transition (p-EMT), rather than complete EMT, poses a higher metastatic risk. Although Fusobacterium nucleatum mainly inhabits in oral cavity, attention has been focused on the F. nucleatum involvement in colorectal cancer development. Here we examined the p-EMT regulation by F. nucleatum in oral squamous cell carcinoma (OSCC) cells. We cultured OSCC cells with epithelial, p-EMT or EMT phenotype with live or heat-inactivated F. nucleatum. Expression of the genes involved in epithelial differentiation, p-EMT and EMT were examined in OSCC cells after co-culture with F. nucleatum by qPCR. Cell growth and invasion of OSCC cells were also examined. Both live and heat-inactivated F. nucleatum upregulated the expression of p-EMT-related genes in OSCC cells with epithelial phenotype, but not with p-EMT or EMT phenotype. Moreover, F. nucleatum promoted invasion of OSCC cells with epithelial phenotype. Co-culture with other strains of bacteria other than Porphyromonas gingivalis did not alter p-EMT-related genes in OSCC cells with epithelial phenotype. F. nucleatum infection may convert epithelial to p-EMT phenotype via altering gene expression in OSCC. Oral hygiene managements against F. nucleatum infection may contribute to reduce the risk for an increase in metastatic ability of OSCC. (Tokushima University Institutional Repository) ● Metadata: 116445 (Link to Publication Site) ● Publication site (DOI): 10.1038/s41598-021-94384-1 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34294795 ● Summary page in Scopus @ Elsevier: 2-s2.0-85111135598 (Tokushima University Institutional Repository: 116445, DOI: 10.1038/s41598-021-94384-1, PubMed: 34294795, Elsevier: Scopus)
19.	Yuri Yoshikawa, Takashi Izawa, Yusaku Hamada, Hiroko Takenaga, Ziyi Wang, Naozumi Ishimaru and Hiroshi Kamioka : Roles for B[a]P and FICZ in subchondral bone metabolism and experimental temporomandibular joint osteoarthritis via the AhR/Cyp1a1 signaling axis., Scientific Reports, Vol.11, No.1, 14927, 2021. (Summary) Bone loss due to smoking represents a major risk factor for fractures and bone osteoporosis. Signaling through the aryl hydrocarbon receptor (AhR) and its ligands contributes to both bone homeostasis and inflammatory diseases. It remains unclear whether the same AhR signaling axis affects the temporomandibular joint (TMJ). The aim of this study was to investigate possible mechanisms which mediate bone loss in the TMJ due to smoking. In particular, whether benzo[a]pyrene (B[a]P), a carcinogen of tobacco smoke, induces expression of the AhR target gene, Cyp1a1, in mandibular condyles. Possible functions of an endogenous ligand of FICZ, were also investigated in a TMJ-osteoarthritis (OA) mouse model. B[a]P was administered orally to wild-type and AhR mice and bone metabolism was subsequently examined. TMJ-OA was induced in wild-type mice with forceful opening of the mouth. Therapeutic functions of FICZ were detected with μCT and histology. Exposure to B[a]P accelerated bone loss in the mandibular subchondral bone. This bone loss manifested with osteoclastic bone resorption and upregulated expression of Cyp1a1 in an AhR-dependent manner. In a mouse model of TMJ-OA, FICZ exhibited a dose-dependent rescue of mandibular subchondral bone loss by repressing osteoclast activity. Meanwhile, in vitro, pre-treatment with FICZ reduced RANKL-mediated osteoclastogenesis. B[a]P regulates mandibular subchondral bone metabolism via the Cyp1a1. The AhR ligand, FICZ, can prevent TMJ-OA by regulating osteoclast differentiation. (Keyword) Animals / Benzo(a)pyrene / Bone Resorption / Carbazoles / Cytochrome P-450 CYP1A1 / Disease Models, Animal / Drug Tapering / gene expression / Mice, Inbred C57BL / Osteoarthritis / Osteogenesis / Receptors, Aryl Hydrocarbon / signal transduction / smoking / temporomandibular joint (Tokushima University Institutional Repository) ● Metadata: 117717 (Link to Publication Site) ● Publication site (DOI): 10.1038/s41598-021-94470-4 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34290363 ● Search Scopus @ Elsevier (PMID): 34290363 ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-021-94470-4 (Tokushima University Institutional Repository: 117717, DOI: 10.1038/s41598-021-94470-4, PubMed: 34290363)
20.	Izumi Ohigashi, Melina Frantzeskakis, Alison Jacques, Sayumi Fujimori, Aya Ushio, Fusano Yamashita, Naozumi Ishimaru, Da Yin, Margaret Cam, C Michael Kelly, Parirokh Awasthi, Kensuke Takada and Yousuke Takahama : The thymoproteasome hardwires the TCR repertoire of CD8+ T cells in the cortex independent of negative selection., The Journal of Experimental Medicine, Vol.218, No.4, 2021. (Summary) The thymoproteasome expressed specifically in thymic cortical epithelium optimizes the generation of CD8+ T cells; however, how the thymoproteasome contributes to CD8+ T cell development is unclear. Here, we show that the thymoproteasome shapes the TCR repertoire directly in cortical thymocytes before migration to the thymic medulla. We further show that the thymoproteasome optimizes CD8+ T cell production independent of the thymic medulla; independent of additional antigen-presenting cells, including medullary thymic epithelial cells and dendritic cells; and independent of apoptosis-mediated negative selection. These results indicate that the thymoproteasome hardwires the TCR repertoire of CD8+ T cells with cortical positive selection independent of negative selection in the thymus. (Tokushima University Institutional Repository) ● Metadata: 116455 (Link to Publication Site) ● Publication site (DOI): 10.1084/jem.20201904 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33555295 ● Search Scopus @ Elsevier (PMID): 33555295 ● Search Scopus @ Elsevier (DOI): 10.1084/jem.20201904 (Tokushima University Institutional Repository: 116455, DOI: 10.1084/jem.20201904, PubMed: 33555295)
21.	Mie Kurosawa, Yosuke Shikama, Masae Furukawa, Rieko Arakaki, Naozumi Ishimaru and Kenji Matsushita : Chemokines Up-Regulated in Epithelial Cells Control Senescence-Associated T Cell Accumulation in Salivary Glands of Aged and Sjögren's Syndrome Model Mice., International Journal of Molecular Sciences, Vol.22, No.5, 2302, 2021. (Summary) Immunosenescence is characterized by age-associated changes in immunological functions. Although age- and autoimmune-related sialadenitis cause dry mouth (xerostomia), the roles of immunosenescence and cellular senescence in the pathogenesis of sialadenitis remain unknown. We demonstrated that acquired immune cells rather than innate immune cells infiltrated the salivary glands (SG) of aged mice. An analysis of isolated epithelial cells from SG revealed that the expression levels of the chemokine CXCL13 were elevated in aged mice. Senescence-associated T cells (SA-Ts), which secrete large amounts of atypical pro-inflammatory cytokines, are involved in the pathogenesis of metabolic disorders and autoimmune diseases. The present results showed that SA-Ts and B cells, which express the CXCL13 receptor CXCR5, accumulated in the SG of aged mice, particularly females. CD4 T cells derived from aged mice exhibited stronger in vitro migratory activity toward CXCL13 than those from young mice. In a mouse model of Sjögren's syndrome (SS), SA-Ts also accumulated in SG, presumably via CXCL12-CXCR4 signaling. Collectively, the present results indicate that SA-Ts accumulate in SG, contribute to the pathogenesis of age- and SS-related sialadenitis by up-regulating chemokines in epithelial cells, and have potential as therapeutic targets for the treatment of xerostomia caused by these types of sialadenitis. (Keyword) Animals / Autoimmune Diseases / B-Lymphocytes / CD4-Positive T-Lymphocytes / Cell Movement / Cellular Senescence / Chemokine CXCL13 / Chemokines / Disease Models, Animal / Epithelial Cells / female / Gene Expression Regulation / male / Mice / Mice, Inbred C57BL / Receptors, CXCR5 / salivary glands / Sialadenitis / Sjögren's syndrome / T lymphocytes / Xerostomia (Tokushima University Institutional Repository) ● Metadata: 117548 (Link to Publication Site) ● Publication site (DOI): 10.3390/ijms22052302 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33669065 ● Search Scopus @ Elsevier (PMID): 33669065 ● Search Scopus @ Elsevier (DOI): 10.3390/ijms22052302 (Tokushima University Institutional Repository: 117548, DOI: 10.3390/ijms22052302, PubMed: 33669065)
22.	Mami Sato, Rieko Arakaki, Hiroaki Tawara, Takaaki Tsunematsu and Naozumi Ishimaru : Formation of Autoimmune Lesions Is Independent of Antibiotic Treatment in NOD Mice., International Journal of Molecular Sciences, Vol.22, No.6, 3239, 2021. (Summary) The relationship between autoimmunity and changes in intestinal microbiota is not yet fully understood. In this study, the role of intestinal microbiota in the onset and progression of autoimmune lesions in non-obese diabetic (NOD) mice was evaluated by administering antibiotics to alter their intestinal microenvironment. Flow cytometric analysis of spleen cells showed that antibiotic administration did not change the proportion or number of T and B cells in NOD mice, and pathological analysis demonstrated that autoimmune lesions in the salivary glands and in the pancreas were also not affected by antibiotic administration. These results suggest that the onset and progression of autoimmunity may be independent of enteral microbiota changes. Our findings may be useful for determining the appropriate use of antibiotics in patients with autoimmune diseases who are prescribed drugs to maintain systemic immune function. (Keyword) Animals / Anti-Bacterial Agents / Autoimmune Diseases / autoimmunity / cytokinesis / Disease Models, Animal / Disease Susceptibility / Immune System / Mice / Mice, Inbred NOD / Sialadenitis (Tokushima University Institutional Repository) ● Metadata: 117463 (Link to Publication Site) ● Publication site (DOI): 10.3390/ijms22063239 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33810172 ● Search Scopus @ Elsevier (PMID): 33810172 ● Search Scopus @ Elsevier (DOI): 10.3390/ijms22063239 (Tokushima University Institutional Repository: 117463, DOI: 10.3390/ijms22063239, PubMed: 33810172)
23.	Takaaki Tsunematsu, Rieko Arakaki, Hidehiko Kawai, Jan Ruppert, Koichi Tsuneyama, Naozumi Ishimaru, C William Earnshaw, Michele Pagano and Yasusei Kudo : is required for the termination of chromosomal passenger complex activity upon mitotic exit., Journal of Cell Science, Vol.133, No.18, 2020. (Summary) terminates CPC activity upon mitotic exit and thereby contributes to proper control of DNA replication. (Tokushima University Institutional Repository) ● Metadata: 115422 (Link to Publication Site) ● Publication site (DOI): 10.1242/jcs.251314 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32934012 ● Summary page in Scopus @ Elsevier: 2-s2.0-85091052907 (Tokushima University Institutional Repository: 115422, DOI: 10.1242/jcs.251314, PubMed: 32934012, Elsevier: Scopus)
24.	Shinya Sento, Yasusei Kudo, Kenji Hibiya, Naozumi Ishimaru, Eri Sasabe, Naoya Kitamura and Tetsuya Yamamoto : Hyalinizing clear cell carcinoma of the anterior lingual salivary gland: A case report and review of the literature, Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, Vol.32, No.4, 267-274, 2020. (Tokushima University Institutional Repository) ● Metadata: 119395 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ajoms.2020.03.002 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-85084530986 (Tokushima University Institutional Repository: 119395, DOI: 10.1016/j.ajoms.2020.03.002, Elsevier: Scopus)
25.	Satoru Kisoda, Wenhua Shao, Natsumi Fujiwara, Yasuhiro Mouri, Takaaki Tsunematsu, Shengjian Jin, Rieko Arakaki, Naozumi Ishimaru and Yasusei Kudo : Prognostic value of partial EMT-related genes in head and neck squamous cell carcinoma by a bioinformatic analysis., Oral Diseases, Vol.26, No.6, 1149-1156, 2020. (Summary) Our findings suggest that p-EMT program may be involved in poor prognosis of HNSCC. SERPINE1, ITGA5, TGFBI, P4HA2, CDH13, and LAMC2 can be used for a prognostic marker. Moreover, HNSCC cells with p-EMT phenotype can be a useful model for investigating a nature of p-EMT. (Tokushima University Institutional Repository) ● Metadata: 114969 (Link to Publication Site) ● Publication site (DOI): 10.1111/odi.13351 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32277532 ● Summary page in Scopus @ Elsevier: 2-s2.0-85083974773 (Tokushima University Institutional Repository: 114969, DOI: 10.1111/odi.13351, PubMed: 32277532, Elsevier: Scopus)
26.	Naito Kurio, Kumiko Kamada, Takumi Kitagawa, Yasusei Kudo, Naozumi Ishimaru and Youji Miyamoto : A case of microcystic adnexal carcinoma arising in the upper gingiva, Japanese Journal of Oral & Maxillofacial Surgery, Vol.66, No.9, 455-459, 2020. (Summary) <p>Microcystic adnexal carcinoma (MAC) is a rare malignant tumor of skin appendages. MAC grows slowly, but is locally aggressive. The metastatic potential is low, but the recurrence rates are very high owing to insufficient dissection. The most common location of MAC is the skin of the midface of middle-aged adults. There has been no report about MAC arising in the gingiva. We report here an extremely rare case of MAC of the upper gingiva in a 53-year-old woman. She presented to our hospital with a 6-year history of a gradually increasing gingival mass. Intraoral examination revealed a smooth, poorly circumscribed mass with white granules resembling Fordyce spots on her upper gingiva. There was no bone destruction or regional lymph node swelling. The histopathological diagnosis was a tumor of skin appendages. Tumor resection was performed. Postoperative pathological examination revealed that the tumor differentiated into hair follicles and the sweat-gland-like structures and deeply infiltrated into muscle, perineural spaces, and bone. Since the surgical margins were positive, additional resection was performed after preoperative mapping biopsy. Finally, the tumor was completely excised. No tumor recurrence or metastasis have been observed over 1 year.</p> (Link to Publication Site) ● Publication site (DOI): 10.5794/jjoms.66.455 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1391975276372989696 ● Search Scopus @ Elsevier (DOI): 10.5794/jjoms.66.455 (DOI: 10.5794/jjoms.66.455, CiNii: 1391975276372989696)
27.	Kanako Yuyama, Yoshitaka Nakamura, Riho Tateyama, Rieko Arakaki, Takuya Tsutsui and Naozumi Ishimaru : Study of the pharmacokinetics of eriodictyol-6-C-β-d-glucoside, a flavonoid of rooibos (Aspalathus linearis) extract, after its oral administration in mice., Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, Vol.1137, 121881, 2019. (Summary) Systemic dry syndrome affects quality of life, and various effective methods are being developed for its treatment. We recently found that rooibos (Aspalathus linearis) extract activates muscarinic M receptor and improves dryness in mice and humans. We identified eriodictyol-6-C-β--glucoside (E6CG) as the active component affecting the secretory functions of exocrine glands; however, the pharmacokinetics and distribution of E6CG in exocrine glands have not been elucidated in mice receiving rooibos extract. We have developed a quantification method using LC-MS/MS to detect E6CG without an internal standard. Experiments on C57BL/6 mice administered rooibos extract showed that E6CG was transferred into blood plasma, with its concentration levels peaking 19.3 min after treatment. Substantial levels of E6CG were detected in the submandibular, sublingual, parotid, and lacrimal glands and in the sweat glands in palm skin. This study reports that rooibos extracts containing E6CG can be used as functional foods for improving systemic dryness. (Keyword) Administration, Oral / Animals / Aspalathus / Flavanones / Glucosides / Limit of Detection / Linear Models / Male / Mice / Mice, Inbred C57BL / Plant Extracts / Reproducibility of Results / Salivary Glands / Skin / Tissue Distribution (Link to Publication Site) ● Publication site (DOI): 10.1016/j.jchromb.2019.121881 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31881511 ● Summary page in Scopus @ Elsevier: 2-s2.0-85076712142 (DOI: 10.1016/j.jchromb.2019.121881, PubMed: 31881511, Elsevier: Scopus)
28.	Aya Miyazaki, Asuna Sugimoto, Keigo Yoshizaki, Keita Kawarabayashi, Kokoro Iwata, Rika Kurogohshi, Takamasa Kitamura, Kunihiro Otsuka, Tomokazu Hasegawa, Yuki Akazawa, Satoshi Fukumoto, Naozumi Ishimaru and Tsutomu Iwamoto : Coordination of WNT signaling and ciliogenesis during odontogenesis by piezo type mechanosensitive ion channel component 1, Scientific Reports, Vol.9, No.1, 14762, 2019. (Summary) Signal transmission from the mechanical forces to the various intracellular activities is a fundamental process during tissue development. Despite their critical role, the mechanism of mechanical forces in the biological process is poorly understood. In this study, we demonstrated that in the response to hydrostatic pressure (HP), the piezo type mechanosensitive ion channel component 1 (PIEZO1) is a primary mechanosensing receptor for odontoblast differentiation through coordination of the WNT expression and ciliogenesis. In stem cells from human exfoliated deciduous teeth (SHED), HP significantly promoted calcium deposition as well as the expression of odontogenic marker genes, PANX3 and DSPP, and WNT related-genes including WNT5b and WNT16, whereas HP inhibited cell proliferation and enhanced primary cilia expression. WNT signaling inhibitor XAV939 and primary cilia inhibitor chloral hydrate blocked the HP-induced calcium deposition. The PIEZO1 activator Yoda1 inhibited cell proliferation but induced ciliogenesis and WNT16 expression. Interestingly, HP and Yoda1 promoted nuclear translocation of RUNX2, whereas siRNA-mediated silencing of PIEZO1 decreased HP-induced nuclear translocation of RUNX2. Taken together, these results suggest that PIEZO1 functions as a mechanotransducer that connects HP signal to the intracellular signalings during odontoblast differentiation. (Tokushima University Institutional Repository) ● Metadata: 114667 (Link to Publication Site) ● Publication site (DOI): 10.1038/s41598-019-51381-9 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31611621 ● Search Scopus @ Elsevier (PMID): 31611621 ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-019-51381-9 (Tokushima University Institutional Repository: 114667, DOI: 10.1038/s41598-019-51381-9, PubMed: 31611621)
29.	Yosuke Shikama, Mie Kurosawa, Masae Furukawa, Naozumi Ishimaru and Kenji Matsushita : Involvement of adiponectin in age-related increases in tear production in mice., Aging, Vol.11, No.19, 8329-8346, 2019. (Summary) Common age-related changes in the human eye contribute to the development of dry eye, including decreases in aqueous tear production. Although the infiltration of lymphocytes into the lacrimal glands occurs with age, age-related increases in tear production have also been observed in mice; however, the mechanisms underlying this increase remain unclear. We herein demonstrated that increases in tear production were not dependent on body weight gain or systemic conditions, such as insulin resistance, using aged mice and high-fat diet-fed mice. The results obtained also showed that senescence-associated T (SA-T) cells accumulated in the lacrimal glands of aged mice, particularly females. Expression levels of the nuclear transcription factor peroxisome proliferator-activated receptor-γ (PPARγ) in whole lacrimal glands and epithelial cells isolated from lacrimal glands were significantly higher in aged mice than in young mice. The expression levels of adiponectin and one of its receptors, AdipoR2, also increased in the lacrimal glands of aged mice, but not in those of high-fat diet-fed mice. Collectively, the present results indicate that PPARγ and adiponectin-mediated signaling contribute to age-related increases in tear production in mice and have potential as therapeutic targets for the treatment of dry eye in humans. (Tokushima University Institutional Repository) ● Metadata: 116268 (Link to Publication Site) ● Publication site (DOI): 10.18632/aging.102322 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31596727 ● Summary page in Scopus @ Elsevier: 2-s2.0-85073646229 (Tokushima University Institutional Repository: 116268, DOI: 10.18632/aging.102322, PubMed: 31596727, Elsevier: Scopus)
30.	Kunihiro Otsuka, Akiko Yamada, Masako Saito, Aya Ushio, Mami Sato, Satoru Kisoda, Wenhua Shao, Takaaki Tsunematsu, Yasusei Kudo, Rieko Arakaki and Naozumi Ishimaru : Ascl2-Regulated Follicular Helper T Cells Promote Autoimmunity in a Murine Model for Sjögren's Syndrome., The American Journal of Pathology, Vol.189, No.12, 2414-2427, 2019. (Summary) mice that received neonatal thymectomy treatment demonstrated that Ascl2 contributes to the Tfh cell differentiation associated with autoimmunity during the early stages independent of Bcl6. In conclusion, our results indicate that abnormal Tfh cell differentiation via Ascl2 regulation might contribute to the pathogenesis of autoimmunity. (Keyword) Animals / Autoantibodies / autoimmunity / B-Lymphocytes / Basic Helix-Loop-Helix Transcription Factors / cell differentiation / Cytokines / Disease Models, Animal / female / Germinal Center / Mice / Mice, Inbred C57BL / Proto-Oncogene Proteins c-bcl-6 / Sjögren's syndrome / T-Lymphocytes, Helper-Inducer (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ajpath.2019.08.008 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31539517 ● Summary page in Scopus @ Elsevier: 2-s2.0-85075213858 (DOI: 10.1016/j.ajpath.2019.08.008, PubMed: 31539517, Elsevier: Scopus)
31.	Rieko Arakaki, Aya Ushio, Satoru Kisoda, Mami Sato, Yoshitaka Nakamura, Kanako Yuyama, Riho Tateyama, Satoru Morishita, Noriyuki Monoi, Yasusei Kudo and Naozumi Ishimaru : Novel effects of rooibos extract on tear and saliva secretion mediated by the muscarinic acetylcholine receptor 3 in mice, Journal of Oral Biosciences, Vol.61, No.3, 179-182, 2019. (Summary) Sicca syndrome is characterized by dry mouth and eyes and results in a reduction of the patient's quality of life. Various natural plants, including certain herbs, have long been employed to alleviate such symptoms. Rooibos grown in South Africa is one of the potent herbal plants used for the treating dry mouth. However, the precise mechanism of action by which rooibos alleviates symptoms of dryness remains unclear. The in vivo effects of rooibos extract (RE), which comprises eriodictyol-6-C-glucoside, on the secretory function of saliva and tears were analyzed after intraoral RE administration using wild-type C57BL/6 (B6) mice. In addition, the mechanisms of RE were investigated after administration of a muscarinic acetylcholine receptor 3 (M3R) antagonist. Tear and saliva volumes in mice increased significantly and in a dose-dependent manner following intraoral RE administration compared to those in mice in the control group administered HO. An experiment performed using darifenacin administration revealed that the effects of RE on secretory function were exerted via M3R. These results suggest that RE administration is an effective treatment for symptoms of dryness and may be used in clinical settings against sicca syndrome. (Keyword) Animals / Aspalathus / Humans / Mice / Mice, Inbred C57BL / Plant Extracts / Quality of Life / Receptors, Muscarinic / Saliva / South Africa (Link to Publication Site) ● Publication site (DOI): 10.1016/j.job.2019.06.001 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31400544 ● Summary page in Scopus @ Elsevier: 2-s2.0-85070548928 (DOI: 10.1016/j.job.2019.06.001, PubMed: 31400544, Elsevier: Scopus)
32.	Rieko Arakaki, Aya Ushio, Kunihiro Otsuka, Yasusei Kudo and Naozumi Ishimaru : A novel method for measuring small amounts of saliva in mice, Oral Science International, Vol.16, No.3, 178-180, 2019. (Link to Publication Site) ● Publication site (DOI): 10.1002/osi2.1013 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-85065772725 (DOI: 10.1002/osi2.1013, Elsevier: Scopus)
33.	牛尾綾, Kunihiro Otsuka, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : CCL22 and autoimmune diseases, Clinical Immunology & Allergology, Vol.71, No.5, 520-526, 2019. (Keyword) C-C motif chemokine 22 (CCL22) / autoimmunity / macrophage / T-cell / Sjogren's syndrome (SS) (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520010378554631296 (CiNii: 1520010378554631296)
34.	Naozumi Ishimaru and Akiko Yamada : Regulatory T cells in Sjogren's syndrome, Journal of Clinical and Experimental Medicine, Vol.268, No.13, 1241-1245, 2019. (Keyword) シェーグレン症候群(SS) / 制御性T細胞(Treg) / 自己免疫病変 / CCR7 / Foxp3 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520854805036527232 (CiNii: 1520854805036527232)
35.	Chihiro Nakatomi, Mitsushiro Nakatomi, Takuma Matsubara, Toshihisa Komori, Takahiro Doi-Inoue, Naozumi Ishimaru, Falk Weih, Tsutomu Iwamoto, Miho Matsuda, Shoichiro Kokabu and Eijiro Jimi : Constitutive activation of the alternative NF-κB pathway disturbs endochondral ossification, Bone, Vol.121, 29-41, 2019. (Keyword) Chondrocytes / alternative NF-kB pathway / endochondral ossification (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bone.2019.01.002 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30611922 ● Summary page in Scopus @ Elsevier: 2-s2.0-85059588595 (DOI: 10.1016/j.bone.2019.01.002, PubMed: 30611922, Elsevier: Scopus)
36.	Aya Ushio, Rieko Arakaki, Kunihiro Ohtsuka, Akiko Yamada, Takaaki Tsunematsu, Yasusei Kudo, Keiko Aota, Masayuki Azuma and Naozumi Ishimaru : CCL22-Producing Resident Macrophages Enhance T Cell Response in Sjögren's Syndrome., Frontiers in Immunology, Vol.9, 2594, 2018. (Summary) Macrophages (MΦs) are critical regulators of immune response and serve as a link between innate and acquired immunity. The precise mechanism of involvement of tissue-resident MΦs in the pathogenesis of autoimmune diseases is not clear. Here, using a murine model for Sjögren's syndrome (SS), we investigated the role of tissue-resident MΦs in the onset and development of autoimmunity. Two unique populations of CD11b and CD11b resident MΦs were observed in the target tissue of the SS model. Comprehensive gene expression analysis of chemokines revealed effective production of CCL22 by the CD11b MΦs. CCL22 upregulated the migratory activity of CD4 T cells by increasing CCR4, a receptor of CCL22, on T cells in the SS model. In addition, CCL22 enhanced IFN-γ production of T cells of the SS model, thereby suggesting that CCL22 may impair the local immune tolerance in the target organ of the SS model. Moreover, administration of anti-CCL22 antibody suppressed autoimmune lesions in the SS model. Finally, histopathological analysis revealed numerous CCL22-producing MΦs in the minor salivary gland tissue specimens of the SS patients. CCL22-producing tissue-resident MΦs may control autoimmune lesions by enhancing T cell response in the SS model. These results suggest that specific chemokines and their receptors may serve as novel therapeutic or diagnostic targets for SS. (Tokushima University Institutional Repository) ● Metadata: 113526 (Link to Publication Site) ● Publication site (DOI): 10.3389/fimmu.2018.02594 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30467506 ● Summary page in Scopus @ Elsevier: 2-s2.0-85056303968 (Tokushima University Institutional Repository: 113526, DOI: 10.3389/fimmu.2018.02594, PubMed: 30467506, Elsevier: Scopus)
37.	Kunihiro Ohtsuka, Kohichi Yamada, Yuhji Taquahashi, Rieko Arakaki, Aya Ushio, Masako Saito, Akiko Yamada, Takaaki Tsunematsu, Yasusei Kudo, Jun Kanno and Naozumi Ishimaru : Long-term polarization of alveolar macrophages to a profibrotic phenotype after inhalation exposure to multi-wall carbon nanotubes., PLoS ONE, Vol.13, No.10, e0205702., 2018. (Summary) Nanomaterials are widely used in various fields. Although the toxicity of carbon nanotubes (CNTs) in pulmonary tissues has been demonstrated, the toxicological effect of CNTs on the immune system in the lung remains unclear. In this study, exposure to Taquann-treated multi-walled CNTs (T-CNTs) was performed using aerosols generated in an inhalation chamber. At 12 months after T-CNT exposure, alveolar inflammation with macrophage accumulation and hypertrophy of the alveolar walls were observed. In addition, fibrotic lesions were enhanced by T-CNT exposure. The macrophages in the bronchoalveolar lavage fluid of T-CNT-exposed mice were not largely shifted to any particular population, and were a mixed phenotype with M1 and M2 polarization. Moreover, the alveolar macrophages of T-CNT-exposed mice produced matrix metalloprotinase-12. These results suggest that T-CNT exposure promoted chronic inflammation and fibrotic lesion formation in profibrotic macrophages for prolonged periods. (Tokushima University Institutional Repository) ● Metadata: 113371 (Link to Publication Site) ● Publication site (DOI): 10.1371/journal.pone.0205702 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30372450 ● Summary page in Scopus @ Elsevier: 2-s2.0-85055616395 (Tokushima University Institutional Repository: 113371, DOI: 10.1371/journal.pone.0205702, PubMed: 30372450, Elsevier: Scopus)
38.	Keiko Aota, Kohichi Kani, Tomoko Yamanoi, Koh-ichi Nakashiro, Naozumi Ishimaru and Masayuki Azuma : Distinct Regulation of CXCL10 Production by Cytokines in Human Salivary Gland Ductal and Acinar Cells., Inflammation, Vol.41, No.4, 1172-1181, 2018. (Summary) CXCL10, a CXC chemokine induced by interferon-gamma [IFN-γ], has been observed in a wide variety of chronic inflammatory disorders and autoimmune conditions. Although CXCL10 is known to be overexpressed in the salivary glands of individuals with primary Sjögren's syndrome (pSS), it is unclear which cells produce CXCL10 under what types of stimulations. Here, we investigated the precise molecular mechanisms by which CXCL10 was produced in human salivary gland ductal (NS-SV-DC) and acinar (NS-SV-AC) cell lines. Our results demonstrated that NS-SV-DC cells produced higher levels of CXCL10 compared to NS-SV-AC cells. In addition, our findings demonstrated that the regulator of the enhancement of CXCL10 was different between NS-SV-DC and NS-SV-AC cells, i.e., interferon-gamma (IFN-γ) had more potential than interferon-alpha (IFN-α), tumor necrosis factor (TNF)-α, and interleukin (IL)1-β in the induction of CXCL10 production in NS-SV-DC cells, whereas TNF-α had potential to induce CXCL10 production in NS-SV-AC cells. A Western blot analysis demonstrated that IFN-γ enhanced the production of CXCL10 via both the JAK/STAT1 pathway and the NF-κB pathway in NS-SV-DC cells, whereas TNF-α enhanced the production of CXCL10 via the NF-κB pathway in NS-SV-AC cells. The results of study suggest that the CXCL10 overexpression in the salivary glands is caused mainly by IFN-γ-stimulated salivary gland ductal cells. The enhanced production of CXCL10 by IFN-γ from ductal cells may result in the inflammation of pSS lesions. (Keyword) Acinar Cells / Cell Line / Chemokine CXCL10 / Cytokines / Humans / Interferon-gamma / NF-kappa B / Salivary Glands / Tumor Necrosis Factor-alpha (Tokushima University Institutional Repository) ● Metadata: 112923 (Link to Publication Site) ● Publication site (DOI): 10.1007/s10753-018-0764-0 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29549479 ● Summary page in Scopus @ Elsevier: 2-s2.0-85044090734 (Tokushima University Institutional Repository: 112923, DOI: 10.1007/s10753-018-0764-0, PubMed: 29549479, Elsevier: Scopus)
39.	Keiko Aota, Tomoko Yamanoi, Kohichi Kani, Koh-ichi Nakashiro, Naozumi Ishimaru and Masayuki Azuma : Inverse correlation between the number of CXCR3+ macrophages and the severity of inflammatory lesions in Sjögren's syndrome salivary glands: a pilot study, Journal of Oral Pathology & Medicine, Vol.47, No.7, 710-718, 2018. (Summary) Mechanisms underlying immune cells' recruitment and activation into the inflammatory lesions of lip salivary glands (LSGs) from primary Sjögren's syndrome (pSS) patients are incompletely understood. Chemokines play pivotal roles in these processes, so we investigated the clinical significance of chemokine receptor CXCR3 and its ligands in the autoimmune lesions of pSS. We histologically determined the grade of LSG samples from 22 patients with pSS and subjected the samples to immunofluorescence analysis to determine the expressions of CXCR3 and its ligands: CXCL9, CXCL10, and CXCL11. To identify the immune cells expressing CXCR3 in the LSGs, we performed double immunofluorescence analysis using antibodies against CD3 (pan-T cells), CD80 (M1 macrophages), CD163 (M2 macrophages), and CD123 (plasmacytoid dendritic cells: pDCs). The relationship between the grade of lymphocytic infiltration and the number of positively stained cells was analyzed by Spearman's rank correlation test. The expressions of CXCL9 and CXCL10 showed particularly intense staining in the LSG samples' ductal cells. The CXCR3 expression was detected mainly in CD80 and CD163 macrophages. The number of CXCR3 CD163 macrophages inversely correlated with the LSG inflammatory lesions' severity (rs = -0.777, P < 0.001). Our results suggest that the enhanced production of CXCL9 and CXCL10 from ductal cells results in the CXCR3 macrophages' migration. There was an inverse correlation between these two parameters: that is, the number of CXCR3 CD163 macrophages decreased as the lymphocytic infiltration grade increased. Although CXCR3 is expressed in all of the innate immune cells, CXCR3 CD163 M2 macrophages may contribute to the anti-inflammatory functions in pSS lesions. (Tokushima University Institutional Repository) ● Metadata: 113977 (Link to Publication Site) ● Publication site (DOI): 10.1111/jop.12756 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29926992 ● Summary page in Scopus @ Elsevier: 2-s2.0-85050503684 (Tokushima University Institutional Repository: 113977, DOI: 10.1111/jop.12756, PubMed: 29926992, Elsevier: Scopus)
40.	Penkhae Utaijaratrasmi, Kulthida Vaeteewoottacharn, Takaaki Tsunematsu, Pranisa Jamjantra, Sopit Wongkham, Chawalit Pairojkul, Narong Khuntikeo, Naozumi Ishimaru, Yongyut Sirivatanauksorn, Ananya Pongpaibul, Peti Thuwajit, Chanitra Thuwajit and Yasusei Kudo : The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes migration of cancer cells., Molecular Cancer, Vol.17, No.1, 2018. (Summary) These findings highlight the miR-15a/PAI-2 axis as a potential therapeutic target in CCA patients. (Tokushima University Institutional Repository) ● Metadata: 113571 (Link to Publication Site) ● Publication site (DOI): 10.1186/s12943-018-0760-x (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29347950 ● Search Scopus @ Elsevier (PMID): 29347950 ● Search Scopus @ Elsevier (DOI): 10.1186/s12943-018-0760-x (Tokushima University Institutional Repository: 113571, DOI: 10.1186/s12943-018-0760-x, PubMed: 29347950)
41.	Mie Kurosawa, Rieko Arakaki, Akiko Yamada, Takaaki Tsunematsu, Yasusei Kudo, J Sprent and Naozumi Ishimaru : NF κB2 Controls the Migratory Activity of Memory T Cells by Regulating Expression of CXCR4 in a Mouse Model of Sjögren's Syndrome, Arthritis & Rheumatology, Vol.69, No.11, 2193-2202, 2017. (Summary) Dysregulated chemokine signaling contributes to autoimmune diseases by facilitating aberrant T cell infiltration into target tissues, but the specific chemokines, receptors, and T cell populations remain largely unidentified. The aim of this study was to examine the role of the potent chemokine CXCL12 and its receptor CXCR4 in the T cell autoimmune response, using alymphoplasia (aly)/aly mice, a model of Sjögren's syndrome (SS). T cell phenotypes in the salivary gland of aly/aly mice were evaluated using immunologic analysis. An in vitro migration assay was used to assess T cell migratory activity toward several chemokines. Gene expression of chemokine receptors and transforming growth factor β receptors (TGFβRs) was measured by quantitative reverse transcription-polymerase chain reaction. The CXCR4 antagonist AMD3100 was administered to the aly/aly mice in order to evaluate its suppressive effect on autoimmune lesions. Effector memory T (TEM) cells derived from aly/aly mice demonstrated higher in vitro migratory activity toward CXCL12 than did TEM cells from aly/+ mice. CXCL12 expression was specifically up-regulated in the SS target cells of aly/aly mice. TEM cells from RelB mice, but not Nfkb1 mice, also showed high migratory activity toward CXCL12, implicating a role of the nonclassical RelB/NF-κB2 pathway in the regulation of TEM cell migration. TEM cells from aly/aly mice also overexpressed TGFβR type I (TGFβRI) and TGFβRII. The CXCR4 antagonist AMD3100 suppressed autoimmune lesions in aly/aly mice by reducing TEM cell infiltration. Our results suggest that the RelB/NF-κB2 pathway regulates T cell migration to autoimmune targets through TGFβ/TGFβR-dependent regulation of CXCL12/CXCR4 signaling. This suggests that these signaling pathways are potential therapeutic targets for the treatment of autoimmune diseases. (Keyword) Animals / Chemokine CXCL12 / Chemotaxis, Leukocyte / Disease Models, Animal / Gene Expression Regulation / In Vitro Techniques / Mice / Mice, Knockout / NF-kappa B p52 Subunit / Receptors, CXCR4 / Sjogren's Syndrome / T-Lymphocytes / Transcription Factor RelB (Tokushima University Institutional Repository) ● Metadata: 111719 (Link to Publication Site) ● Publication site (DOI): 10.1002/art.40230 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28804991 ● Summary page in Scopus @ Elsevier: 2-s2.0-85031674261 (Tokushima University Institutional Repository: 111719, DOI: 10.1002/art.40230, PubMed: 28804991, Elsevier: Scopus)
42.	Hidesuke Tada, Natsumi Fujiwara, Takaaki Tsunematsu, Yoshiko Tada, Rieko Arakaki, Naofumi Tamaki, Naozumi Ishimaru and Yasusei Kudo : Preventive effects of mouthguard use while sleeping on recurrent aphthous stomatitis: Preliminary interventional study., Clinical and Experimental Dental Research, Vol.3, No.5, 198-203, 2017. (Summary) Recurrent aphthous stomatitis (RAS) is the most common inflammatory ulceration in the oral mucosa of otherwise healthy individuals and is often accompanied by severe pain. However, the etiology of RAS is not completely understood, and currently, no therapy can completely prevent RAS recurrence. In our clinical experience, we noticed that patients using a night guard, which is often used for bruxism treatment, did not develop RAS. Therefore, the aim of this study was to determine whether mouthguard use can suppress RAS development. The cohort of this interventional, prospective, single-center, and self-controlled study included 20 subjects who developed RAS at least once a month. The oral health of all the subjects was recorded for 60 days before and after intervention with a mouthguard. The average number of RAS incidences decreased from 5.5 to 1.0, the average days until healing decreased from 7.3 to 5.6, and the period with RAS decreased from 31.5 to 5.0 with mouthguard use. Mouthguard use may be beneficial for preventing RAS development. (Tokushima University Institutional Repository) ● Metadata: 111727 (Link to Publication Site) ● Publication site (DOI): 10.1002/cre2.88 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29744201 ● Search Scopus @ Elsevier (PMID): 29744201 ● Search Scopus @ Elsevier (DOI): 10.1002/cre2.88 (Tokushima University Institutional Repository: 111727, DOI: 10.1002/cre2.88, PubMed: 29744201)
43.	Takashi Izawa, Rieko Arakaki and Naozumi Ishimaru : Role of Fas and RANKL signaling in peripheral immune tolerance, Journal of Clinical & Cellular Immunology, Vol.8, No.4, 512, 2017. (Keyword) Fas / T cell / apoptosis / dendritic cell / RANKL / autoimmunity (Link to Publication Site) ● Publication site (DOI): 10.4172/2155-9899.1000512 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.4172/2155-9899.1000512 (DOI: 10.4172/2155-9899.1000512)
44.	Mina Kozai, Yuki Kubo, Tomoya Katakai, Hiroyuki Kondo, Hiroshi Kiyonari, Karin Schaeuble, Sanjiv A. Luther, Naozumi Ishimaru, Izumi Ohigashi and Yousuke Takahama : Essential role of CCL21 in establishment of central self-tolerance in T cells, The Journal of Experimental Medicine, Vol.214, No.7, 1925-1935, 2017. (Summary) The chemokine receptor CCR7 directs T cell relocation into and within lymphoid organs, including the migration of developing thymocytes into the thymic medulla. However, how three functional CCR7 ligands in mouse, CCL19, CCL21Ser, and CCL21Leu, divide their roles in immune organs is unclear. By producing mice specifically deficient in CCL21Ser, we show that CCL21Ser is essential for the accumulation of positively selected thymocytes in the thymic medulla. CCL21Ser-deficient mice were impaired in the medullary deletion of self-reactive thymocytes and developed autoimmune dacryoadenitis. T cell accumulation in the lymph nodes was also defective. These results indicate a nonredundant role of CCL21Ser in the establishment of self-tolerance in T cells in the thymic medulla, and reveal a functional inequality among CCR7 ligands in vivo. (Keyword) Animals / Autoimmune Diseases / Central Tolerance / Chemokine CCL21 / Dacryocystitis / Flow Cytometry / gene expression / Lymph Nodes / Mice, Inbred C57BL / knockout mice / Mice, Nude / Mice, Transgenic / Microscopy, Confocal / Receptors, CCR7 / Reverse Transcriptase Polymerase Chain Reaction / Self Tolerance / T lymphocytes / Thymocytes / Thymus Gland (Tokushima University Institutional Repository) ● Metadata: 110168 (Link to Publication Site) ● Publication site (DOI): 10.1084/jem.20161864 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28611158 ● Search Scopus @ Elsevier (PMID): 28611158 ● Search Scopus @ Elsevier (DOI): 10.1084/jem.20161864 (Tokushima University Institutional Repository: 110168, DOI: 10.1084/jem.20161864, PubMed: 28611158)
45.	Aya Ushio, Rieko Arakaki, Hiroshi Eguchi, Fumika Hotta, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : Pathological Analysis of Ocular Lesions in a Murine Model of Sjögren's Syndrome., International Journal of Molecular Sciences, Vol.18, No.6, 2017. (Summary) Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by severe inflammation of exocrine glands such as the salivary and lacrimal glands. When it affects the lacrimal glands, many patients experience keratoconjunctivitis due to severely dry eyes. This study investigated the pathological and immunological characteristics of ocular lesions in a mouse model of SS. Corneal epithelial injury and hyperplasia were confirmed pathologically. The number of conjunctival mucin-producing goblet cells was significantly decreased in the SS model mice compared with control mice. Expression levels of transforming growth factor (TGF)-, interleukin (IL)-6, tumor necrosis factor (TNF)-, and C-X-C motif chemokine (CXCL) 12 were significantly higher in the corneal epithelium of the SS model mice than in control mice. Inflammatory lesions were observed in the Harderian, intraorbital, and extraorbital lacrimal glands in the SS model mice, suggesting that the ocular glands were targeted by an autoimmune response. The lacrimal glands of the SS model mice were infiltrated by cluster of differentiation (CD)4+ T cells. Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed significantly increased mRNA expression of TNF-, TGF-, CXCL9, and lysozyme in the extraorbital lacrimal glands of the SS model mice compared with control mice. These results add to the understanding of the complex pathogenesis of SS and may facilitate development of new therapeutic strategies. (Tokushima University Institutional Repository) ● Metadata: 111713 (Link to Publication Site) ● Publication site (DOI): 10.3390/ijms18061209 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28587293 ● Search Scopus @ Elsevier (PMID): 28587293 ● Search Scopus @ Elsevier (DOI): 10.3390/ijms18061209 (Tokushima University Institutional Repository: 111713, DOI: 10.3390/ijms18061209, PubMed: 28587293)
46.	Takashi Izawa, Rieko Arakaki and Naozumi Ishimaru : Crosstalk between cytokine RANKL and AhR signaling in osteoclasts controls bone homeostasis, Journal of Cytokine Biology, Vol.2, No.2, 114, 2017. (Keyword) RANKL / AhR / osteoclast (Link to Publication Site) ● Publication site (DOI): 10.4172/2576-3881.1000114 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.4172/2576-3881.1000114 (DOI: 10.4172/2576-3881.1000114)
47.	Yosuke Shikama, Yasusei Kudo, Naozumi Ishimaru and Makoto Funaki : Potential Role of Free Fatty Acids in the Pathogenesis of Periodontitis and Primary Sjögren's Syndrome., International Journal of Molecular Sciences, Vol.18, No.4, 2017. (Summary) Clinical studies have shown that metabolic disorders such as type 2 diabetes and dyslipidemia are associated with increased risk of oral-related diseases, such as periodontitis and Sjögren's syndrome. Although changes in the immune system are critical in both of these metabolic disorders and oral-related diseases, the mechanism underlying the interaction between these diseases remains largely unknown. Obesity and type 2 diabetes are known to be associated with higher concentrations of free fatty acids in blood. Among free fatty acids, saturated fatty acids such as palmitic acid have been demonstrated to induce inflammatory responses mainly via the innate immune systems, and to be involved in the pathogenesis of type 2 diabetes in tissues such as adipose tissue, liver, pancreas, and skeletal muscle. Here, we highlight recent advances in evidence for the potential involvement of palmitic acid in the pathogenesis of periodontitis and Sjögren's syndrome, and discuss the possibility that improvement of the lipid profile could be a new strategy for the treatment of these diseases. (Keyword) Animals / Cytokines / Fatty Acids, Nonesterified / Humans / Inflammation Mediators / Lipid Metabolism / Palmitic Acid / Periodontitis / Sjogren's Syndrome (Tokushima University Institutional Repository) ● Metadata: 112408 (Link to Publication Site) ● Publication site (DOI): 10.3390/ijms18040836 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28420093 ● Search Scopus @ Elsevier (PMID): 28420093 ● Search Scopus @ Elsevier (DOI): 10.3390/ijms18040836 (Tokushima University Institutional Repository: 112408, DOI: 10.3390/ijms18040836, PubMed: 28420093)
48.	Satoko Kujiraoka, Takaaki Tsunematsu, Yukiko Sato, Maki Yoshida, Ayataka Ishikawa, Rei Tohyama, Michio Tanaka, Yutaka Kobayashi, Tomoyuki Kondo, Aya Ushio, Kunihiro Otsuka, Mie Kurosawa, Masako Saito, Akiko Yamada, Rieko Arakaki, Hirokazu Nagai, Hiromasa Nikai, Kengo Takeuchi, Toshitaka Nagao, Youji Miyamoto, Naozumi Ishimaru and Yasusei Kudo : Establishment and characterization of a clear cell odontogenic carcinoma cell line with EWSR1-ATF1 fusion gene., Oral Oncology, Vol.69, 46-55, 2017. (Summary) To the best of our knowledge, this is the first report on the establishment of a CCOC cell line. CCOC-T cells serve as a useful in vitro model for understanding the pathogenesis and nature of MOT. (Tokushima University Institutional Repository) ● Metadata: 111726 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.oraloncology.2017.04.003 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28559020 ● Search Scopus @ Elsevier (PMID): 28559020 ● Search Scopus @ Elsevier (DOI): 10.1016/j.oraloncology.2017.04.003 (Tokushima University Institutional Repository: 111726, DOI: 10.1016/j.oraloncology.2017.04.003, PubMed: 28559020)
49.	Akiko Yamada, Rieko Arakaki, Masako Saito, Yasusei Kudo and Naozumi Ishimaru : Dual Role of Fas/FasL-Mediated Signal in Peripheral Immune Tolerance., Frontiers in Immunology, Vol.8, No.403, 2017. (Summary) Fas-mediated apoptosis contributes to physiological and pathological cellular processes, such as differentiation and survival. In particular, the roles of Fas in immune cells are complex and critical for the maintenance of immune tolerance. The precise pathways and unique functions associated with Fas/FasL-mediated signaling in the immune system are known. The dual character of Fas/FasL-mediated immune regulation that induces beneficial or harmful effects is associated with the onset or development of immune disorders. Studies on mutations in genes encoding Fas and FasL gene of humans and mice contributed to our understanding of the pathogenesis of autoimmune diseases. Here, we review the opposing functions of Fas/FasL-mediated signaling, bilateral effects of Fas/FasL on in immune cells, and complex pathogenesis of autoimmunity mediated by Fas/FasL. (Tokushima University Institutional Repository) ● Metadata: 110975 (Link to Publication Site) ● Publication site (DOI): 10.3389/fimmu.2017.00403 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28424702 ● Search Scopus @ Elsevier (PMID): 28424702 ● Search Scopus @ Elsevier (DOI): 10.3389/fimmu.2017.00403 (Tokushima University Institutional Repository: 110975, DOI: 10.3389/fimmu.2017.00403, PubMed: 28424702)
50.	Takashi Izawa, Rieko Arakaki, Hiroki Mori, Takaaki Tsunematsu, Yasusei Kudo, Eiji Tanaka and Naozumi Ishimaru : The nuclear receptor AhR controls bone homeostasis by regulating osteoclast differentiation via the RANK/c-Fos signaling axis., The Journal of Immunology, Vol.197, No.12, 4639-4650, 2016. (Summary) The aryl hydrocarbon receptor (AhR) pathway plays a key role in receptor activator of NF-κB ligand (RANKL)-mediated osteoclastogenesis. However, the mechanism underlying the regulation of AhR expression in osteoclasts and the signaling pathway through which AhR controls osteoclastogenesis remain unclear. We found that the expression of AhR in bone marrow-derived osteoclasts was upregulated by RANKL at an earlier stage than was the expression of signature osteoclast genes such as those encoding cathepsin K and NFAT, cytoplasmic, calcineurin-dependent 1. In response to RANKL, bone marrow macrophages isolated from AhR(-/-) mice exhibited impaired phosphorylation of Akt and MAPK as well as NF-κB, whereas their response to M-CSF remained unchanged. Osteoclast differentiation mediated by the AhR signaling pathway was also regulated in an RANKL/c-Fos-dependent manner. Furthermore, ligand activation of AhR by the smoke toxin benzo[a]pyrene accelerated osteoclast differentiation in a receptor-dependent manner, and AhR-dependent regulation of mitochondrial biogenesis in osteoclasts was observed. Moreover, AhR(-/-) mice exhibited impaired bone healing with delayed endochondral ossification. Taken together, the present results suggest that the RANKL/AhR/c-Fos signaling axis plays a critical role in osteoclastogenesis, thereby identifying the potential of AhR in treating pathological, inflammatory, or metabolic disorders of the bone. (Link to Publication Site) ● Publication site (DOI): 10.4049/jimmunol.1600822 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27849171 ● Search Scopus @ Elsevier (PMID): 27849171 ● Search Scopus @ Elsevier (DOI): 10.4049/jimmunol.1600822 (DOI: 10.4049/jimmunol.1600822, PubMed: 27849171)
51.	Takaaki Tsunematsu, Natsumi Fujiwara, Maki Yoshida, Yukihiro Takayama, Satoko Kujiraoka, Guangying Qi, Masae Kitagawa, Tomoyuki Kondo, Akiko Yamada, Rieko Arakaki, Mutsumi Miyauchi, Ikuko Ogawa, Yoshihiro Abiko, Hiroki Nikawa, Shinya Murakami, Takashi Takata, Naozumi Ishimaru and Yasusei Kudo : Human odontogenic epithelial cells derived from epithelial rests of Malassez possess stem cell properties., Laboratory Investigation; a Journal of Technical Methods and Pathology, 2016. (Summary) Epithelial cell rests of Malassez (ERM) are quiescent epithelial remnants of the Hertwig's epithelial root sheath (HERS) that are involved in the formation of tooth roots. ERM cells are unique epithelial cells that remain in periodontal tissues throughout adult life. They have a functional role in the repair/regeneration of cement or enamel. Here, we isolated odontogenic epithelial cells from ERM in the periodontal ligament, and the cells were spontaneously immortalized. Immortalized odontogenic epithelial (iOdE) cells had the ability to form spheroids and expressed stem cell-related genes. Interestingly, iOdE cells underwent osteogenic differentiation, as demonstrated by the mineralization activity in vitro in mineralization-inducing media and formation of calcification foci in iOdE cells transplanted into immunocompromised mice. These findings suggest that a cell population with features similar to stem cells exists in ERM and that this cell population has a differentiation capacity for producing calcifications in a particular microenvironment. In summary, iOdE cells will provide a convenient cell source for tissue engineering and experimental models to investigate tooth growth, differentiation, and tumorigenesis.Laboratory Investigation advance online publication, 1 August 2016; doi:10.1038/labinvest.2016.85. (Tokushima University Institutional Repository) ● Metadata: 113576 (Link to Publication Site) ● Publication site (DOI): 10.1038/labinvest.2016.85 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27479086 ● Search Scopus @ Elsevier (PMID): 27479086 ● Search Scopus @ Elsevier (DOI): 10.1038/labinvest.2016.85 (Tokushima University Institutional Repository: 113576, DOI: 10.1038/labinvest.2016.85, PubMed: 27479086)
52.	Chieko Sugawara, Akira Takahashi, Fumiaki Kawano, Yasusei Kudo, Naozumi Ishimaru and Youji Miyamoto : Intraoral Ultrasonography of Tongue Mass Lesions, Dento Maxillo Facial Radiology, Vol.45, No.5, 20150362, 2016. (Summary) To demonstrate the usefulness of intraoral ultrasonography (IOUS) for tongue mass lesions, we analyzed surgery cases excluding squamous-cell carcinoma and leukoplakia and compared IOUS and pathological findings. We used the hospital information system and Radiology Information System to evaluate the IOUS and pathological findings of patients who underwent surgeries for tongue masses in the past 11 years. Surgeries for the tongues were performed in 268 cases. Imaging examinations were carried out in 52 (19.4%) cases including 42 (15.7%) cases by IOUS. The pathological results of the surgeries were as follows: 36 cases were inflammatory lesions, 74 cases were tumours, 131 cases were hyperplasia, 8 cases were cystic lesions and 19 cases were other miscellaneous lesions. On the other hand, the number of patients who received IOUS in the same period was 87, and 42 of them had surgeries. In 32 out of the 42 (76.2%) cases, pre-operative IOUS features matched with pathological results. Most of the haemangiomas and lipomas could be diagnosed by IOUS alone. IOUS of the tongue revealed the nature of the lesions including the border, size, location, depth, the presence or absence of a capsule and the internal structure including vascularity of the mass. The ultrasonographic findings well reflected the histological findings. IOUS is a simple and useful technique that provides additional information beyond inspection, clarifying the internal structure, blood flow and relationships with the adjacent tissues. In this article, we indicated 11 representative cases (fibrous polyp, haemangioma, pyogenic granuloma, lipoma, liposarcoma, chondroma, lymphangioma, schwannoma, neurofibroma, pleomorphic adenoma and amyloidosis) to show the usefulness of IOUS. (Keyword) ultrasound (Tokushima University Institutional Repository) ● Metadata: 111906 (Link to Publication Site) ● Publication site (DOI): 10.1259/dmfr.20150362 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26915405 ● Search Scopus @ Elsevier (PMID): 26915405 ● Search Scopus @ Elsevier (DOI): 10.1259/dmfr.20150362 (Tokushima University Institutional Repository: 111906, DOI: 10.1259/dmfr.20150362, PubMed: 26915405)
53.	Akiko Yamada, Aya Ushio, Rieko Arakaki, Takaaki Tsunematsu, Yasusei Kudo, Yoshio Hayashi and Naozumi Ishimaru : Impaired expansion of regulatory T cells in a neonatal thymectomy-induced autoimmune mouse model., The American Journal of Pathology, Vol.185, No.11, 2886-2897, 2015. (Summary) Neonatal thymectomy in certain mouse strains is known to induce organ-specific autoimmunity due to impaired functions of T cells, including Foxp3(+) regulatory T (Treg) cells in the thymus. The precise mechanism underlying the induction of autoimmunity by neonatal thymectomy remains unclear. One possibility is that depletion of Treg cells breaks down peripheral tolerance. We examined the functions of Treg cells by using a murine Sjögren syndrome model of NFS/sld mice that underwent neonatal thymectomy. The ratio of Treg cells to effector memory phenotype T cells in thymectomy mice was significantly lower than that of nonthymectomy mice. In addition, in vitro induction of peripherally induced Treg cells by transforming growth factor-β (TGF-β) using naive T cells from Sjögren syndrome model mice was severely impaired. The mRNA expression of TGF-β receptor I and II and Smad3 and -4 in the TGF-β-induced signal transduction pathway of Treg cells in this Sjögren syndrome model were lower than those of control mice. In addition, Treg cells in this Sjögren syndrome model exhibited an interferon-γ-producing Th1-like phenotype that resembled effector T cells. In conclusion, these results suggest that abnormal expansion and differentiation of Treg cells and inflammatory cytokines produced by Treg cells contribute to the development of autoimmunity. (Keyword) Animals / Animals, Newborn / Autoimmunity / Cell Differentiation / Cytokines / Disease Models, Animal / Female / Interferon-gamma / Mice / Mice, Inbred C57BL / Mutation / Protein-Serine-Threonine Kinases / Receptors, Transforming Growth Factor beta / Specific Pathogen-Free Organisms / T-Lymphocytes, Regulatory / Thymectomy / Transforming Growth Factor beta (Tokushima University Institutional Repository) ● Metadata: 113529 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ajpath.2015.07.007 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26343329 ● Search Scopus @ Elsevier (PMID): 26343329 ● Search Scopus @ Elsevier (DOI): 10.1016/j.ajpath.2015.07.007 (Tokushima University Institutional Repository: 113529, DOI: 10.1016/j.ajpath.2015.07.007, PubMed: 26343329)
54.	Takaaki Tsunematsu, Rieko Arakaki, Akiko Yamada, Naozumi Ishimaru and Yasusei Kudo : The non-canonical role of Aurora-A in DNA replication., Frontiers in Oncology, Vol.96, No.4, 468-480, 2015. (Summary) Aurora-A is a well-known mitotic kinase that regulates mitotic entry, spindle formation, and chromosome maturation as a canonical role. During mitosis, Aurora-A protein is stabilized by its phosphorylation at Ser51 via blocking anaphase-promoting complex/cyclosome-mediated proteolysis. Importantly, overexpression and/or hyperactivation of Aurora-A is involved in tumorigenesis via aneuploidy and genomic instability. Recently, the novel function of Aurora-A for DNA replication has been revealed. In mammalian cells, DNA replication is strictly regulated for preventing over-replication. Pre-replication complex (pre-RC) formation is required for DNA replication as an initiation step occurring at the origin of replication. The timing of pre-RC formation depends on the protein level of geminin, which is controlled by the ubiquitin-proteasome pathway. Aurora-A phosphorylates geminin to prevent its ubiquitin-mediated proteolysis at the mitotic phase to ensure proper pre-RC formation and ensuing DNA replication. In this review, we introduce the novel non-canonical role of Aurora-A in DNA replication. (Tokushima University Institutional Repository) ● Metadata: 110980 (Link to Publication Site) ● Publication site (DOI): 10.3389/fonc.2015.00187 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26380219 ● Search Scopus @ Elsevier (PMID): 26380219 ● Search Scopus @ Elsevier (DOI): 10.3389/fonc.2015.00187 (Tokushima University Institutional Repository: 110980, DOI: 10.3389/fonc.2015.00187, PubMed: 26380219)
55.	Tomomi Sano, Misaki Iwashita, Nagayasu Nagayasu, Akiko Yamashita, Takanori Shinjo, Atsushi Hashikata, Tomoichiro Asano, Akifumi Kushiyama, Naozumi Ishimaru, Yousuke Takahama and Fusanori Nishimura : Protection from diet-induced obesity and insulin resistance in mice lacking CCL19-CCR7 signaling., Obesity, Vol.23, No.7, 1460-1471, 2015. (Summary) Several chemokines play important roles in recruiting the monocyte/macrophage lineage into adipose tissues. We previously found CCL19 was highly expressed in adipocytes cocultured with macrophages stimulated by endotoxin. This study aimed to evaluate the role of CCL19-CCR7 axis on obesity and insulin resistance. Serum CCL19 concentration was examined in obese model mice challenged by endotoxin. CCL19 receptor-null, Ccr7(-/-), mice and wild-type mice fed a high-fat diet or normal diet were used to investigate the role of CCL19 signals on obesity-associated inflammation. CCL19 protein was elevated in the sera of obese model mice challenged by endotoxin. Ccr7(-/-) mice were protected from diet-induced obesity and insulin resistance. The adipose tissue and liver expression of inflammatory genes of Ccr7(-/-) mice was much lower than in diet-induced obese mice. Ccr7(-/-) mice were protected from fatty liver and dyslipidemia and exhibited increased thermogenesis on high-fat feeding. CCL19 attracts activated dendritic cells (DC). The expression of the DC markers, CD11b and 11c, was not observed in the adipose tissues of Ccr7(-/-) mice fed a high-fat diet, which might be closely associated with the protection of these mice from obesity. The CCL19-CCR7 pathway associates with the development of high-fat-induced obesity and insulin resistance. (Link to Publication Site) ● Publication site (DOI): 10.1002/oby.21127 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26097021 ● Summary page in Scopus @ Elsevier: 2-s2.0-84933178175 (DOI: 10.1002/oby.21127, PubMed: 26097021, Elsevier: Scopus)
56.	Tomoyoshi Yamano, J Nedjic, M Hinteberger, S Koser, S Pinto, N Gerdes, E Lutgens, Naozumi Ishimaru, M Busslinger, B Brors, B Kyewski and L Klein : Intrathymic B cell licensing for Aire expression and T cell tolerance induction., Immunity, Vol.42, No.6, 1048-1061, 2015. (Summary) Thymic antigen-presenting cells (APCs) such as dendritic cells and medullary thymic epithelial cells (mTECs) use distinct strategies of self-antigen expression and presentation to mediate central tolerance. The thymus also harbors B cells; whether they also display unique tolerogenic features and how they genealogically relate to peripheral B cells is unclear. Here, we found that Aire is expressed in thymic but not peripheral B cells. Aire expression in thymic B cells coincided with major histocompatibility class II (MHCII) and CD80 upregulation and immunoglobulin class-switching. These features were recapitulated upon immigration of naive peripheral B cells into the thymus, whereby this intrathymic licensing required CD40 signaling in the context of cognate interactions with autoreactive CD4(+) thymocytes. Moreover, a licensing-dependent neo-antigen selectively upregulated in immigrating B cells mediated negative selection through direct presentation. Thus, autoreactivity within the nascent T cell repertoire fuels a feed forward loop that endows thymic B cells with tolerogenic features. (Keyword) Animals / Antigen Presentation / Antigens, CD40 / Antigens, CD80 / Autoantigens / B-Lymphocytes / CD4-Positive T-Lymphocytes / Cell Differentiation / Cells, Cultured / Central Tolerance / Clonal Selection, Antigen-Mediated / Histocompatibility Antigens Class II / Humans / Immunoglobulin Class Switching / Mice / Mice, Inbred BALB C / Mice, Knockout / Signal Transduction / Thymus Gland / Transcription Factors (Link to Publication Site) ● Publication site (DOI): 10.1016/j.immuni.2015.05.013 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26070482 ● Summary page in Scopus @ Elsevier: 2-s2.0-84937631527 (DOI: 10.1016/j.immuni.2015.05.013, PubMed: 26070482, Elsevier: Scopus)
57.	Yosuke Shikama, Yasusei Kudo, Naozumi Ishimaru and Makoto Funaki : Possible involvement of palmitate in pathogensis of periodontitis., Journal of Cellular Physiology, Vol.230, No.12, 2981-2989, 2015. (Summary) Type 2 diabetes (T2D) is characterized by decreased insulin sensitivity and higher concentrations of free fatty acids (FFAs) in plasma. Among FFAs, saturated fatty acids (SFAs), such as palmitate, have been suggested to promote inflammatory responses. Although many epidemiological studies have shown a link between periodontitis and T2D, little is known about the clinical significance of SFAs in periodontitis. In this study, we showed that gingival fibroblasts have cell-surface expression of CD36, which is also known as FAT/fatty acid translocase. Moreover, CD36 expression was increased in gingival fibroblasts of high-fat diet-induced T2D model mice, compared with gingival fibroblasts of mice fed a normal diet. DNA microarray analysis revealed that palmitate increased mRNA expression of pro-inflammatory cytokines and chemokines in human gingival fibroblasts (HGF). Consistent with these results, we confirmed that palmitate-induced interleukin (IL)-6, IL-8, and CXCL1 secretion in HGF, using a cytokine array and ELISA. SFAs, but not an unsaturated fatty acid, oleate, induced IL-8 production. Docosahexaenoic acid (DHA), which is one of the omega-3 polyunsaturated fatty acids, significantly suppressed palmitate-induced IL-6 and IL-8 production. Treatment of HGF with a CD36 inhibitor also inhibited palmitate-induced pro-inflammatory responses. Finally, we demonstrated that Porphyromonas gingivalis (P.g.) lipopolysaccharide and heat-killed P.g. augmented palmitate-induced chemokine secretion in HGF. These results suggest a potential link between SFAs in plasma and the pathogenesis of periodontitis. J. Cell. Physiol. 230: 2981-2989, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. (Link to Publication Site) ● Publication site (DOI): 10.1002/jcp.25029 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25921577 ● Summary page in Scopus @ Elsevier: 2-s2.0-84939824337 (DOI: 10.1002/jcp.25029, PubMed: 25921577, Elsevier: Scopus)
58.	Nurul Md. Islam, Shinsuke Itoh, Takeshi Yanagita, Kumi Sumiyoshi, Satoru Hayano, Koh-Ichi Kuremoto, Hiroshi Kurosaka, Tadashi Honjo, Noriaki Kawanabe, Hiroshi Kamioka, Takayoshi Sakai, Naozumi Ishimaru, Ichiro Taniuchi and Takashi Yamashiro : Runx/Cbfb signaling regulates postnatal development of granular convoluted tubule in the mouse submandibular gland., Developmental Dynamics, Vol.244, No.3, 488-496, 2015. (Summary) The rodent salivary gland is not fully developed at birth and the cellular definitive differentiation takes place postnatally. However, little is known about its molecular mechanism. Here we provide the loss-of-function genetic evidence that Runx signaling affects postnatal development of the submandibular gland (SMG). Core binding factor β (Cbfb) is a cotranscription factor which forms a heterodimer with Runx proteins. Cbfb was specifically expressed in the duct epithelium, specifically in the SMG. Epithelial Cbfb deficiency resulted in decrease in the size of the SMG and in the saliva secretion on postnatal day 35. The Cbfb mutant SMG specifically exhibited involution of the granular convoluted tubules (GCT), with a down-regulated expression of its marker genes, such as Klk1, Ngf, and Egf. The induction of GCT is under the control of androgens, and the Cbfb mutant SMG demonstrated down-regulated expression of Crisp3, an androgen-dependent transcript. Because the circulating testosterone or tissue dihydrotestosterone levels were not affected in the Cbfb mutants, it appears that Runx/Cbfb signaling regulate androgen receptor pathway, but does not affect the circulating testosterone levels or the enzymatic conversion to DHT. Runx signaling is important in the postnatal development of androgen-dependent GCT in the SMG. (Link to Publication Site) ● Publication site (DOI): 10.1002/dvdy.24231 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25410786 ● Summary page in Scopus @ Elsevier: 2-s2.0-84924058978 (DOI: 10.1002/dvdy.24231, PubMed: 25410786, Elsevier: Scopus)
59.	Akihiko Iwasa, Rieko Arakaki, Naoko Honma, Aya Ushio, Akiko Yamada, Tomoyuki Kondo, Emi Kurosawa, Satoko Kujiraoka, Takaaki Tsunematsu, Yasusei Kudo, Eiji Tanaka, Noriko Yoshimura, Nobuhiro Harada, Yoshio Hayashi and Naozumi Ishimaru : Aromatase controls Sjögren syndrome-like lesions through monocyte chemotactic protein-1 in target organ and adipose tissue-associated macrophages., The American Journal of Pathology, Vol.185, No.1, 151-161, 2015. (Summary) Several autoimmune diseases are known to develop in postmenopausal women. However, the mechanism by which estrogen deficiency influences autoimmunity is unknown. Aromatase is an enzyme that converts androgens to estrogens. Herein, we used female aromatase gene knockout (ArKO) mice as a model of estrogen deficiency to investigate the molecular mechanism that underlies the onset and development of autoimmunity. Histological analyses showed that inflammatory lesions in the lacrimal and salivary glands of ArKO mice increased with age. Adoptive transfer of spleen cells or bone marrow cells from ArKO mice into recombination activating gene 2 knockout mice failed to induce the autoimmune lesions. Expression of mRNA encoding proinflammatory cytokines and monocyte chemotactic protein-1 increased in white adipose tissue of ArKO mice and was significantly higher than that in wild-type mice. Moreover, an increased number of inflammatory M1 macrophages was observed in white adipose tissue of ArKO mice. A significantly increased monocyte chemotactic protein-1 mRNA expression of the salivary gland tissue in ArKO was found together with adiposity. Furthermore, the autoimmune lesions in a murine model of Sjögren syndrome were exacerbated by administration of an aromatase inhibitor. These results suggest that aromatase may play a key role in the pathogenesis of Sjögren syndrome-like lesions by controlling the target organ and adipose tissue-associated macrophage. (Tokushima University Institutional Repository) ● Metadata: 113532 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ajpath.2014.09.006 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25447050 ● Summary page in Scopus @ Elsevier: 2-s2.0-84918779178 (Tokushima University Institutional Repository: 113532, DOI: 10.1016/j.ajpath.2014.09.006, PubMed: 25447050, Elsevier: Scopus)
60.	Chieko Sugawara, Akira Takahashi, Fumiaki Kawano, Takaharu Kudoh, Akiko Yamada, Naozumi Ishimaru, Hara Kanae and Youji Miyamoto : Neuroendocrine tumor in the mandible: a case report with imaging and histopathologic findings, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Vol.119, No.1, e41-e48, 2015. (Summary) Neuroendocrine tumors (NETs) arise from neuroendocrine cells and are mostly observed in the gastrointestinal tract, pancreas, and lungs. NETs in the oral and maxillofacial region are extremely rare. We report a case of a 59-year-old woman with an NET in the mandible. The patient did not show any symptoms except for remarkable swelling and bleeding. The lesion appeared as a radiolucent honeycomb abnormality with bone destruction on panoramic radiography. The histopathologic diagnosis following a biopsy was NET. Contrast-enhanced computed tomography (CT), (18)F-fluorodeoxyglucose positron emission computed tomography ((18)F-FDG PET/CT), and adrenal scintigraphy-labeled meta-iodobenylguanidine were the modalities added to identify the primary site. Multiple lesions were confirmed in the gastrointestinal tract. Endoscopy was performed to identify the lesions, and several lesions were observed protruding from the mucous membranes. However, the endoscopy specimens did not yield an accurate diagnosis because adequate samples were not acquired. Blood and urine tests revealed no functional activity caused by the tumors. Although the origin was not histopathologically confirmed with endoscopy, this patient was situationally diagnosed with nonfunctional NET originating from the duodenum, as demonstrated by the metastases in the mandible. (Keyword) neuroendocrine tumor / neuroendocrine carcinoma / oral cavity / synaptophysin / chromogranin A (Link to Publication Site) ● Publication site (DOI): 10.1016/j.oooo.2014.09.024 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25459356 ● Summary page in Scopus @ Elsevier: 2-s2.0-84915767535 (DOI: 10.1016/j.oooo.2014.09.024, PubMed: 25459356, Elsevier: Scopus)
61.	Rieko Arakaki, Hiroshi Eguchi, Akiko Yamada, Yasusei Kudo, Akihiko Iwasa, Enkhmaa Tserennadmid, Hotta Fumika, Mitamura-Aizawa Sayaka, Yoshio Hayashi and Naozumi Ishimaru : Anti-Inflammatory Effects of Rebamipide Eyedrop Administration on Ocular Lesions in a Murine Model of Primary Sjögren's Syndrome., PLoS ONE, Vol.9, No.5, e98390, 2014. (Summary) Topical therapy is effective for dry eye, and its prolonged effects should help in maintaining the quality of life of patients with dry eye. We previously reported that the oral administration of rebamipide (Reb), a mucosal protective agent, had a potent therapeutic effect on autoimmune lesions in a murine model of Sjögren's syndrome (SS). However, the effects of topical treatment with Reb eyedrops on the ocular lesions in the murine model of SS are unknown. Reb eyedrops were administered to the murine model of SS aged 4-8 weeks four times daily. Inflammatory lesions of the extraorbital and intraorbital lacrimal glands and Harderian gland tissues were histologically evaluated. The direct effects of Reb on the lacrimal glands were analyzed using cultured lacrimal gland cells. Tear secretions of Reb-treated mice were significantly increased compared with those of untreated mice. In addition to the therapeutic effect of Reb treatment on keratoconjunctivitis, severe inflammatory lesions of intraorbital lacrimal gland tissues in this model of SS were resolved. The mRNA expression levels of IL-10 and mucin 5Ac in conjunctival tissues from Reb-treated mice was significantly increased compared with those of control mice. Moreover, lactoferrin production from lacrimal gland cells was restored by Reb treatment. Topical Reb administration had an anti-inflammatory effect on the ocular autoimmune lesions in the murine model of SS and a protective effect on the ocular surfaces. (Keyword) Administration, Ophthalmic / Alanine / Animals / Anti-Inflammatory Agents / Cells, Cultured / Disease Models, Animal / Drug Administration Schedule / Female / Gene Expression Regulation / Humans / Interleukin-10 / Keratoconjunctivitis / Lacrimal Apparatus / Lactoferrin / Mice / Mucin 5AC / Quinolones / Sjogren's Syndrome (Tokushima University Institutional Repository) ● Metadata: 110973 (Link to Publication Site) ● Publication site (DOI): 10.1371/journal.pone.0098390 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24866156 ● Summary page in Scopus @ Elsevier: 2-s2.0-84901407753 (Tokushima University Institutional Repository: 110973, DOI: 10.1371/journal.pone.0098390, PubMed: 24866156, Elsevier: Scopus)
62.	Ashrin Nur Meinar, Rieko Arakaki, Akiko Yamada, Tomoyuki Kondo, Mie Kurosawa, Yasusei Kudo, Megumi Watanabe, Tetsuo Ichikawa, Yoshio Hayashi and Naozumi Ishimaru : A critical role for thymic stromal lymphopoietin in nickel-induced allergy in mice., The Journal of Immunology, Vol.192, No.9, 4025-4031, 2014. (Summary) Ni is the most frequent cause of contact allergy induced by metals. However, the underlying mechanism of this induction is unknown. Our previous research demonstrates that activation of dendritic cells (DCs) through p38MAPK/MKK6 is required for Ni-induced allergy in mice. In the current study, we investigated the cellular and molecular mechanisms underlying Ni-induced allergy using a mouse model that involves injecting Ni into the ear, with or without Freund's incomplete or complete adjuvants. Nickel had greater potential to cause allergic reactions compared with palladium and gold. Among the proteins expressed at higher levels in mice with Ni-induced allergy, we focused on thymic stromal lymphopoietin (TSLP), which is produced in abundance by keratinocytes. We detected increased expression of the TSLP receptor (TSLPR) in DCs from cervical lymph nodes of mice with Ni-induced allergy, suggesting that DCs in ear tissues were activated through TSLPR signaling induced by keratinocyte-derived TSLP. Furthermore, delayed-type hypersensitivity reactions in mice with Ni-induced allergy were decreased significantly by injection of a Tslp-short interfering RNA along with atelocollagen in the ear skin. These results suggest that Ni allergy may be triggered by a TSLP/TSLPR-mediated interaction between epithelial and immune cells. (Keyword) Animals / Blotting, Western / Cytokines / Dendritic Cells / Disease Models, Animal / Enzyme-Linked Immunosorbent Assay / Female / Flow Cytometry / Hypersensitivity / Immunoglobulins / immunohistochemistry / Mice / Mice, Inbred C57BL / Nickel / Oligonucleotide Array Sequence Analysis / RNA, Small Interfering / Real-Time Polymerase Chain Reaction / Receptors, Cytokine / Reverse Transcriptase Polymerase Chain Reaction (Link to Publication Site) ● Publication site (DOI): 10.4049/jimmunol.1300276 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24670797 ● Summary page in Scopus @ Elsevier: 2-s2.0-84899557087 (DOI: 10.4049/jimmunol.1300276, PubMed: 24670797, Elsevier: Scopus)
63.	Kouta Yano, Christine Carter, Naofumi Yoshida, Takaya Abe, Akiko Yamada, Takeshi Nitta, Naozumi Ishimaru, Kensuke Takada, W Geoffrey Butcher and Yousuke Takahama : Gimap3 and Gimap5 cooperate to maintain T-cell numbers in the mouse., European Journal of Immunology, Vol.44, No.2, 561-572, 2014. (Summary) Gimap3 (IAN4) and Gimap5 (IAN5) are highly homologous GTP-binding proteins of the Gimap family. Gimap3 and Gimap5, whose transcripts are abundant in mature lymphocytes, can associate with antiapoptotic Bcl-2 family proteins. While it is established that Gimap5 regulates T-cell survival, the in vivo role of Gimap3 is unclear. Here we report the preparation and characteristics of mouse strains lacking Gimap3 and/or Gimap5. We found that the number of T cells was markedly reduced in mice deficient in both Gimap3 and Gimap5. The defects in T-cell cellularity were more severe in mice lacking both Gimap3 and Gimap5 than in mice lacking only Gimap5. No defects in the cellularity of T cells were detected in mice lacking only Gimap3, whereas bone marrow cells from Gimap3-deficient mice showed reduced T-cell production in a competitive hematopoietic environment. Moreover, retroviral overexpression and short hairpin RNAs-mediated silencing of Gimap3 in bone marrow cells elevated and reduced, respectively, the number of T cells produced in irradiated mice. These results suggest that Gimap3 is a regulator of T-cell numbers in the mouse and that multiple Gimap family proteins cooperate to maintain T-cell survival. (Tokushima University Institutional Repository) ● Metadata: 105966 (Link to Publication Site) ● Publication site (DOI): 10.1002/eji.201343750 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24510501 ● Summary page in Scopus @ Elsevier: 2-s2.0-84893530167 (Tokushima University Institutional Repository: 105966, DOI: 10.1002/eji.201343750, PubMed: 24510501, Elsevier: Scopus)
64.	Tomokazu Hasegawa, Yuki Akazawa, Hirokazu Nagai, Takamasa Kitamura, Naozumi Ishimaru, Kimiko Ueda Yamaguchi, Hiroshi Nakagawa, Yukiko Kori, Aimi Yamamoto and Tsutomu Iwamoto : Capillary Hemangioma on Palate of Infant:Case Report, The Japanese Journal of Pediatric Dentistry, Vol.52, No.3, 448-453, 2014. (Summary) A hemangioma frequently occurs on the tongue, lip, buccal mucosa, and gingiva in the oral region,though it relatively rarely seen on the palate. We report a case of capillary hemangioma found on the palate of a 2-year-10-month-old boy. He was referred to our department with the chief complaint of a tumor on the palate and a hemangioma was noted on the palatal side of the upper deciduous incisors.We performed surgical resection and the mass was extirpated. The postoperative course was uneventful. Although there was no evidence of recurrence at 6 months after surgery, careful follow-up examinations will be necessary until the upper permanent incisors erupt. (Keyword) 血管腫 / 口蓋 / 幼児期 (Link to Publication Site) ● Publication site (DOI): 10.11411/jspd.52.3_448 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390282680495239168 ● Search Scopus @ Elsevier (DOI): 10.11411/jspd.52.3_448 (DOI: 10.11411/jspd.52.3_448, CiNii: 1390282680495239168)
65.	Keiko Aota, Yoshiko Yamamura, Kohichi Kani, Hideyuki Takano, Katsumi Motegi, Yukihiro Momota, Naozumi Ishimaru and Masayuki Azuma : Prevention of the destruction of acinar structure in patients with Sjogren's syndrome : Clinicopathological study on the effectiveness of cepharanthin, Journal of The Japanese Stomatological Society, Vol.62, No.4, 254-261, 2013. (Summary) Sjögren's syndrome (SS) is characterized by the eventual total replacement of the acinar structure by marked infiltration of lymphocytes into the salivary and lacrimal glands. We previously demonstrated that tumor necrosis factor-α (TNF-α) induced matrix metalloproteinase-9 (MMP-9) production by the stimulating transcription factor, nuclear factor-κB (NF-κB), in human salivary gland acinar cells and that cepharanthin, a biscoclaurine alkaloid, prevented the activation of TNF-α-induced NF-κB activity. In addition, we have shown that cepharanthin prevented the destruction of acinar tissues in murine SS. Thus, in this study, we investigated the clinicopathological effect of cepharanthin on the patients with SS. <br>Ten patients with a diagnosis of primary SS were enrolled in this study. They were treated with cepharanthin for three months, followed by the evaluation of salivary production, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-SS-A antibody, anti-SS-B antibody, pathological examination of labial salivary gland biopsy specimens, and the symptom of drymouth. <br>Average salivary production was 4.25ml/10minutes before the study. This average production increased to 6.46ml/10minutes after the study. There were no remarkable changes in CRP, ESR, anti-SS-A antibody and anti-SS-B antibody. In pathological findings, although the decreases in infiltration of lymphocytes were observed in 5 out of 5 cases, the reduction of destruction of acinar structures was clearly detected in 5 cases. Improvement of symptom of drymouth was detected in 7 out of 10 cases. <br>These observations suggest that cepharanthin treatment might provide an efficient and useful therapeutic approach for countering the destruction of acinar tissue in salivary glands of patients with SS. (Keyword) Sjogren'ssyndrome(Sjogren症候群) / cepharanthin(セファランチン) / salivaryglandacinarcell(唾液腺腺房細胞) (Link to Publication Site) ● Publication site (DOI): 10.11277/stomatology.62.254 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390001206436002048 ● Search Scopus @ Elsevier (DOI): 10.11277/stomatology.62.254 (DOI: 10.11277/stomatology.62.254, CiNii: 1390001206436002048)
66.	Emi Kawakami, Nobuhiko Kawai, Nao Kinouchi, Hiroyo Mori, Yutaka Ohsawa, Naozumi Ishimaru, Yoshihide Sunada, Sumihare Noji and Eiji Tanaka : Local applications of myostatin-siRNA with atelocollagen increase skeletal muscle mass and recovery of muscle function., PLoS ONE, Vol.8, No.5, 2013. (Summary) These data suggest local administration of Mst-siRNA/ATCOL complex could lead to skeletal muscle hypertrophy and recovery of motor disability in mCAV-3Tg mice. Therefore, ATCOL-mediated application of siRNA is a potential tool for therapeutic use in muscular atrophy diseases. (Link to Publication Site) ● Publication site (DOI): 10.1371/journal.pone.0064719 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23717655 ● Search Scopus @ Elsevier (PMID): 23717655 ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0064719 (DOI: 10.1371/journal.pone.0064719, PubMed: 23717655)
67.	Natsumi Shimizu, Izumi Nakako Nakajima, Takaaki Tsunematsu, Ikuko Ogawa, Hidehiko Kawai, Ryoichi Hirayama, Akira Fujimori, Akiko Yamada, Ryuichi Okayasu, Naozumi Ishimaru, Takashi Takata and Yasusei Kudo : Selective enhancing effect of early mitotic inhibitor 1 depletion on the sensitivity of doxorubicin or X-ray treatment in human cancer cells., The Journal of Biological Chemistry, 2013. (Summary) Chemotherapy and radiation in addition to surgery has proven useful in a number of different cancer types, but the effectiveness in normal tissue cannot be avoided in these therapies. To improve the effectiveness of these therapies selectively in cancer tissue is important for avoiding side-effects. Early mitotic inhibitor 1 (Emi1) is known to have the function to inhibit anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex, which ubiquitylates the cell cycle related proteins. It recently has been shown that Emi1 knockdown prevents transition from S to G2 phase by downregulating geminin via APC/C activation. At present anticancer drugs for targeting DNA synthesis to interfere with rapidly dividing cells commonly are used. As Emi1 depletion interferes with completion of DNA synthesis in cancer cells, we thought that Emi1 knockdown might enhance the sensitivity for anticancer agents. Here we confirmed that Emi1 siRNA induced polyploidy for preventing transition from S to G2 phase in several cancer cell lines. Then, we treated Emi1 depleted cells with doxorubicin. Interestingly, increased apoptotic cells were observed after doxorubicin treatment in Emi1 siRNA treated cancer cells. In addition, Emi1 depletion enhanced the sensitivity of X-rays irradiation in cancer cells. Importantly, synergistic effect of Emi1 knockdown in these combination therapies was not observed in normal cells. These results suggest that Emi1 siRNA can be a useful tool for enhancing of sensitivity of cancer cells to anticancer reagents and radiation. (Tokushima University Institutional Repository) ● Metadata: 113579 (Link to Publication Site) ● Publication site (DOI): 10.1074/jbc.M112.446351 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23645673 ● Search Scopus @ Elsevier (PMID): 23645673 ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.M112.446351 (Tokushima University Institutional Repository: 113579, DOI: 10.1074/jbc.M112.446351, PubMed: 23645673)
68.	Yosuke Shikama, Naozumi Ishimaru, Yasusei Kudo, Yukiko Bandou, N Aki, Yoshio Hayashi and Makoto Funaki : Effects of Free Fatty Acids on Human Salivary Gland Epithelial Cells., Journal of Dental Research, Vol.92, No.6, 540-546, 2013. (Summary) Obesity and type 2 diabetes (T2D) are characterized by decreased insulin sensitivity and higher concentrations of free fatty acids (FFAs) in plasma. Among FFAs, saturated fatty acids (SFAs), such as palmitate, have been proposed to promote inflammatory responses. Primary Sjögren's syndrome (SS) is an autoimmune disease characterized by inflammatory mononuclear cell infiltration and destruction of epithelial cells in the salivary and lacrimal glands. IL-6 production and -fodrin degradation are increased in salivary gland epithelial cells of patients with primary SS. Although previous studies have shown a link between SS and either dyslipidemia or T2D, little is known about the clinical significance of FFAs in primary SS. Here we report that SFAs, but not unsaturated fatty acids, induced IL-6 production via NF-B and p38 MAPK activation in human salivary gland epithelial cells. Moreover, palmitate induced apoptosis and -fodrin degradation by caspase-3 activation. Unlike salivary gland epithelial cells, induction of IL-6 production and the degradation of -fodrin in response to palmitate were undetectable in squamous carcinoma cells and keratinocytes. Taken together, SFAs induced IL-6 production and -fodrin degradation in salivary gland epithelial cells, implicating a potential link between the pathogenesis of primary SS and SFAs level in plasma. (Link to Publication Site) ● Publication site (DOI): 10.1177/0022034513487378 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23603335 ● Search Scopus @ Elsevier (PMID): 23603335 ● Search Scopus @ Elsevier (DOI): 10.1177/0022034513487378 (DOI: 10.1177/0022034513487378, PubMed: 23603335)
69.	Ritsuko 徳永律子 Oura, Rieko Arakaki, Akiko Yamada, Yasusei Kudo, Eiji Tanaka, Yoshio Hayashi and Naozumi Ishimaru : Induction of Rapid T Cell Death and Phagocytic Activity by Fas-Deficient lpr Macrophages., The Journal of Immunology, 2013. (Summary) Peripheral T cells are maintained by the apoptosis of activated T cells through the Fas-Fas ligand system. Although it is well known that normal T cells fail to survive in the Fas-deficient immune condition, the molecular mechanism for the phenomenon has yet to be elucidated. In this study, we demonstrate that rapid cell death and clearance of normal T cells were induced by Fas-deficient lpr macrophages. Transfer of normal T cells into lpr mice revealed that Fas expression on donor T cells was promptly enhanced through the IFN-/IFN-R. In addition, Fas ligand expression and phagocytic activity of lpr macrophages were promoted through increased NF-B activation. Controlling Fas expression on macrophages plays an essential role in maintaining T cell homeostasis in the peripheral immune system. Our data suggest a critical implication to the therapeutic strategies such as transplantation and immunotherapy for immune disorder or autoimmunity related to abnormal Fas expression. (Link to Publication Site) ● Publication site (DOI): 10.4049/jimmunol.1103794 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23255359 ● Search Scopus @ Elsevier (PMID): 23255359 ● Search Scopus @ Elsevier (DOI): 10.4049/jimmunol.1103794 (DOI: 10.4049/jimmunol.1103794, PubMed: 23255359)
70.	Takaaki Tsunematsu, Yoshihiro Takihara, Naozumi Ishimaru, Michele Pagano, Takashi Takata and Yasusei Kudo : Aurora-A controls pre-replicative complex assembly and DNA replication by stabilizing geminin in mitosis., Nature Communications, Vol.4, 2013. (Summary) Geminin, an essential factor for DNA replication, directly binds to the licensing factor Cdt1 and inhibits pre-replicative complex formation to prevent re-replication. In G1, geminin levels are controlled by the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase complex, which targets geminin for proteasomal degradation to allow pre-replicative complex formation. Conversely, from S to G2, geminin is stabilized due to APC/C ubiquitin ligase complex inhibition, ensuring the inhibition of pre-replicative complex formation. However, mitotic regulation of geminin has hitherto not been described. Here we show that Aurora-A phosphorylates geminin on Thr25 during M phase, and this event induces geminin stabilization by preventing its APC/C ubiquitin ligase complex-mediated degradation during mitosis. In turn, stabilized geminin inhibits SCF(Skp2)-mediated degradation of Cdt1 to ensure pre-replicative complex formation in the ensuing S phase. The Aurora-A-geminin-Cdt1 axis therefore represents a critical regulator of proper DNA replication. (Tokushima University Institutional Repository) ● Metadata: 113580 (Link to Publication Site) ● Publication site (DOI): 10.1038/ncomms2859 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23695679 ● Search Scopus @ Elsevier (PMID): 23695679 ● Search Scopus @ Elsevier (DOI): 10.1038/ncomms2859 (Tokushima University Institutional Repository: 113580, DOI: 10.1038/ncomms2859, PubMed: 23695679)
71.	Takashi Izawa, Tomoyuki Kondo, Mie Kurosawa, Ritsuko 徳永律子 Oura, Kazuma Matsumoto, Eiji Tanaka, Akiko Yamada, Rieko Arakaki, Yasusei Kudo, Yoshio Hayashi and Naozumi Ishimaru : Fas-Independent T-Cell Apoptosis by Dendritic Cells Controls Autoimmune Arthritis in MRL/lpr Mice, PLoS ONE, Vol.7, No.12, e48798, 2012. (Summary) BACKGROUND: Although autoimmunity in MRL/lpr mice occurs due to a defect in Fas-mediated cell death of T cells, the role of Fas-independent apoptosis in pathogenesis has rarely been investigated. We have recently reported that receptor activator of nuclear factor (NF)-B ligand (RANKL)-activated dendritic cells (DCs) play a key role in the pathogenesis of rheumatoid arthritis (RA) in MRL/lpr mice. We here attempted to establish a new therapeutic strategy with RANKL-activated DCs in RA by controlling apoptosis of peripheral T cells. Repeated transfer of RANKL-activated DCs into MRL/lpr mice was tested to determine whether this had a therapeutic effect on autoimmunity. METHODS AND FINDING: Cellular and molecular mechanisms of Fas-independent apoptosis of T cells induced by the DCs were investigated by in vitro and in vivo analyses. We demonstrated that repeated transfers of RANKL-activated DCs into MRL/lpr mice resulted in therapeutic effects on RA lesions and lymphoproliferation due to declines of CD4(+) T, B, and CD4(-)CD8(-) double negative (DN) T cells. We also found that the Fas-independent T-cell apoptosis was induced by a direct interaction between tumor necrosis factor (TNF)-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) on T cells and TRAIL on Fas-deficient DCs in MRL/lpr mice. CONCLUSION: These results strongly suggest that a novel Fas-independent apoptosis pathway in T cells maintains peripheral tolerance and thus controls autoimmunity in MRL/lpr mice. (Tokushima University Institutional Repository) ● Metadata: 110974 (Link to Publication Site) ● Publication site (DOI): 10.1371/journal.pone.0048798 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23300516 ● Search Scopus @ Elsevier (PMID): 23300516 ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0048798 (Tokushima University Institutional Repository: 110974, DOI: 10.1371/journal.pone.0048798, PubMed: 23300516)
72.	Natsumi Takamaru, Daisuke Uchida, Go Ohe, Hirokazu Nagai, Naozumi Ishimaru and Youji Miyamoto : A case of giant cell epulis accompanied by bone formation in the premolar region of the mandible, Japanese Journal of Oral & Maxillofacial Surgery, Vol.58, No.11, 651-654, 2012. (Summary) Giant cell epulis (peripheral giant cell granuloma) is a granuloma consisting of a large number of multinucleated giant cells. Its incidence is high in Europe and the United States, but is very low in Japan. Giant cell epulis accompanied by bone formation is extremely rare in Japan. We report a case of giant cell epulis accompanied by bone formation. A 46-year-old woman visited our hospital because of a mass in the left mandibular molar region. There was a well-demarcated, pedunculated mass in the left mandibular molar region. The mass was excised under the clinical diagnosis of epulis. Histopathologically, the resected specimen consisted of spindle cells resembling fibroblasts and many multinucleated giant cells. Moreover, newly synthesized bone was observed in the center of the mass. The pathological diagnosis was a giant cell granuloma. Two years six months after the operation, there has been no evidence of recurrence. (Keyword) giant cell epulis(巨細胞エプーリス) / giant cell epulis(キョサイボウエプーリス) / bone formation(骨形成) / bone formation(ホネケイセイ) (Link to Publication Site) ● Publication site (DOI): 10.5794/jjoms.58.651 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390282681509153536 ● Search Scopus @ Elsevier (DOI): 10.5794/jjoms.58.651 (DOI: 10.5794/jjoms.58.651, CiNii: 1390282681509153536)
73.	Chieko Sugawara, Akira Takahashi, Michiko Kubo, Hideki Otsuka, Naozumi Ishimaru, Youji Miyamoto and Eiichi Honda : Preoperative evaluation of patients with squamous cell carcinoma of the oral cavity: fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography and ultrasonography versus histopathology., Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Vol.114, No.4, 516-525, 2012. (Summary) PET/CT and US are complementary tools to evaluate preoperative patients. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.oooo.2012.06.004 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22986248 ● Search Scopus @ Elsevier (PMID): 22986248 ● Search Scopus @ Elsevier (DOI): 10.1016/j.oooo.2012.06.004 (DOI: 10.1016/j.oooo.2012.06.004, PubMed: 22986248)
74.	Yasusei Kudo, Shinji Iizuka, Maki Yoshida, Takaaki Tsunematsu, Tomoyuki Kondo, Ajiravudh Subarnbhesaj, Mohamed Elsayed Deraz, Bsm Samadarani Siriwardena, Hidetoshi Tahara, Naozumi Ishimaru, Ikuko Ogawa and Takashi Takata : Matrix metalloproteinase-13 (MMP-13) directly and indirectly promotes tumor angiogenesis., The Journal of Biological Chemistry, 2012. (Summary) Matrix metalloproteinases (MMPs) are extracellular zinc-dependent endopeptidases involved in the degradation and remodeling of extracellular matrix (ECM) in physiological and pathological processes. MMPs also have a role in cell proliferation, migration, differentiation, angiogenesis and apoptosis. We previously identified cancer invasion-related factors by comparing the gene expression profiles between parent and highly invasive clone of cancer cells. Matrix metalloproteinase-13 (MMP-13) was identified as a common upregulated gene by cancer invasion-related factors. Although MMP-13 slightly promoted tumor invasion, we found that MMP-13 was involved in tumor angiogenesis. Conditioned media from MMP-13-overexpressing cells promoted capillary formation of immortalized human umbilical vein endothelial cells (HUVECs). Furthermore, treatment with recombinant MMP-13 protein enhanced capillary tube formation both in vitro and in vivo. MMP-13-promoted capillary tube formation was mediated by activation of focal adhesion kinase (FAK) and ERK. Interestingly, MMP-13 promoted the secretion of VEGF-A from fibroblasts and endothelial cells. By immunohistochemical analysis, we found a possible correlation between MMP-13 expression and the number of blood vessels in human cancer cases. In summary, these findings suggest that MMP-13 may directly and indirectly promote tumor angiogenesis. (Tokushima University Institutional Repository) ● Metadata: 113581 (Link to Publication Site) ● Publication site (DOI): 10.1074/jbc.M112.373159 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22992737 ● Search Scopus @ Elsevier (PMID): 22992737 ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.M112.373159 (Tokushima University Institutional Repository: 113581, DOI: 10.1074/jbc.M112.373159, PubMed: 22992737)
75.	Yasusei Kudo, Shinji Iizuka, Maki Yoshida, Thao Phuong Nguyen, M Samadarani B S Siriwardena, Takaaki Tsunematsu, Mariko Ohbayashi, Toshinori Ando, Daijiro Hatakeyama, Toshiyuki Shibata, Keiichi Koizumi, Masahiro Maeda, Naozumi Ishimaru, Ikuko Ogawa and Takashi Takata : Periostin directly and indirectly promotes tumor lymphangiogenesis of head and neck cancer., PLoS ONE, Vol.7, No.8, e44488, 2012. (Summary) Our findings suggest that periostin itself as well as periostin-induced upregulation of VEGF-C may promote lymphangiogenesis. We suggest that periostin may be a marker for prediction of malignant behaviors in HNSCC and a potential target for future therapeutic intervention to obstruct tumoral lymphatic invasion and lymphangiogenesis in HNSCC patients. (Tokushima University Institutional Repository) ● Metadata: 113582 (Link to Publication Site) ● Publication site (DOI): 10.1371/journal.pone.0044488 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22952986 ● Search Scopus @ Elsevier (PMID): 22952986 ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0044488 (Tokushima University Institutional Repository: 113582, DOI: 10.1371/journal.pone.0044488, PubMed: 22952986)
76.	Naozumi Ishimaru, Akiko Yamada, Takeshi Nitta, Rieko Arakaki, Martin Lipp, Yousuke Takahama and Yoshio Hayashi : CCR7 with S1P1 signaling through AP-1 for migration of Foxp3+ regulatory T-cells controls autoimmune exocrinopathy., The American Journal of Pathology, Vol.180, No.1, 199-208, 2012. (Summary) Forkhead box p3-positive (Foxp3(+)) regulatory T cells (T(reg) cells) participate in maintaining peripheral immune tolerance and suppressing autoimmunity. We recently reported that in situ patrolling by C-C-chemokine receptor 7 (CCR7)(+) T(reg) cells in target organs is essential for controlling autoimmune lesions in Sjögren's syndrome. In the present study, the molecular mechanism underlying CCR7-mediated T(reg) cell migration was investigated in a mouse model. The impaired migratory response of Ccr7(-/-) T(reg) cells to sphingosine 1-phosphate (S1P) occurred because of defective association of S1P receptor 1 (S1P(1)) with a G coupled-protein. In addition, T-cell receptor (TCR)- and S1P(1)-mediated Ras-related C3 botulinum toxin substrate 1 (Rac-1), extracellular signal-related kinase (ERK), and c-Jun phosphorylation required for activator protein 1 (AP-1) transcriptional activity were significantly impaired in Ccr7(-/-) T(reg) cells. Surprisingly, the abnormal nuclear localization of Foxp3 was detected after abrogation of the c-Jun and Foxp3 interaction in the nucleus of Ccr7(-/-) T(reg) cells. These results indicate that CCR7 essentially controls the migratory function of T(reg) cells through S1P(1)-mediated AP-1 signaling, which is regulated through its interaction with Foxp3 in the nucleus. (Keyword) Animals / Autoimmune Diseases / Cell Movement / Chemotaxis / Exocrine Glands / Forkhead Transcription Factors / JNK Mitogen-Activated Protein Kinases / Lysophospholipids / MAP Kinase Signaling System / Mice / Mice, Inbred C57BL / Receptors, CCR7 / Signal Transduction / Sphingosine / T-Lymphocytes, Regulatory / Transcription Factor AP-1 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ajpath.2011.09.027 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22067914 ● Search Scopus @ Elsevier (PMID): 22067914 ● Search Scopus @ Elsevier (DOI): 10.1016/j.ajpath.2011.09.027 (DOI: 10.1016/j.ajpath.2011.09.027, PubMed: 22067914)
77.	Megumi Watanabe, Naozumi Ishimaru, Meinar Nur Ashrin, Rieko Arakaki, Akiko Yamada, Tetsuo Ichikawa and Yoshio Hayashi : A Novel DC Therapy with Manipulation of MKK6 Gene on Nickel Allergy in Mice, PLoS ONE, Vol.6, No.4, E19017, 2011. (Summary) BACKGROUND: Although the activation of dermal dendritic cells (DCs) or Langerhans cells (LCs) via p38 mitogen-activated protein kinase (MAPK) plays a crucial role in the pathogenesis of metal allergy, the in vivo molecular mechanisms have not been identified and a possible therapeutic strategy using the control of dermal DCs or LCs has not been established. In this study, we focused on dermal DCs to define the in vivo mechanisms of metal allergy pathogenesis in a mouse nickel (Ni) allergy model. The effects of DC therapy on Ni allergic responses were also investigated. METHODS AND FINDING: The activation of dermal DCs via p38 MAPK triggered a T cell-mediated allergic immune response in this model. In the MAPK signaling cascade in DCs, Ni potently phosphorylated MAP kinase kinase 6 (MKK6) following increased DC activation. Ni-stimulated DCs could prime T cell activation to induce Ni allergy. Interestingly, when MKK6 gene-transfected DCs were transferred into the model mice, a more pronounced allergic reaction was observed. In addition, injection of short interfering (si) RNA targeting the MKK6 gene protected against a hypersensitivity reaction after Ni immunization. The cooperative action between T cell activation and MKK6-mediated DC activation by Ni played an important role in the development of Ni allergy. CONCLUSIONS: DC activation by Ni played an important role in the development of Ni allergy. Manipulating the MKK6 gene in DCs may be a good therapeutic strategy for dermal Ni allergy. (Keyword) Animals / Blotting, Western / Female / Flow Cytometry / Hypersensitivity / Immunohistochemistry / Langerhans Cells / MAP Kinase Kinase 6 / Mice / Mice, Inbred C57BL / Microscopy, Confocal / Nickel / RNA, Small Interfering (Link to Publication Site) ● Publication site (DOI): 10.1371/journal.pone.0019017 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21544193 ● Search Scopus @ Elsevier (PMID): 21544193 ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0019017 (DOI: 10.1371/journal.pone.0019017, PubMed: 21544193)
78.	T Yamano, S Watanabe, H Hasegawa, T Suzuki, R Abe, H Tahara, T Nitta, Naozumi Ishimaru, J Sprent and H Kishimoto : Ex-vivo expanded DC induce donor-specific central and peripheral tolerance and prolong the acceptance of donor skin allografts., Blood, Vol.117, No.9, 2640-2648, 2011. (Summary) Dendritic cells (DCs) are known to regulate immune responses by inducing both central and peripheral tolerance. DCs play a vital role in negative selection of developing thymocytes by deleting T cells with high-affinity for self-peptide-major histocompatibility complexes. In the periphery, DCs mediate peripheral tolerance by promoting regulatory T-cell development, induction of T-cell unresponsiveness, and deletion of activated T cells. We studied whether allogeneic DCs, obtained from bone marrow cultured with either Flt3L (FLDCs) or granulocyte-macrophage colony-stimulating factor (GMDCs), could induce allospecific central and peripheral tolerance after IV injection; B cells were used as a control. The results showed that only FLDCs reached the thymus after injection and that these cells induced both central and peripheral tolerance to donor major histocompatibility complexes. For central tolerance, injection of FLDCs induced antigen-specific clonal deletion of both CD8 and CD4 single-positive thymocytes. For peripheral tolerance, injection of FLDCs induced donor-specific T-cell unresponsiveness and prolonged survival of donor-derived skin grafts. Tolerance induction by adoptive transfer of FLDCs could be a useful approach for promoting graft acceptance after organ transplantation. (Keyword) Adoptive Transfer / Animals / Cell Movement / Cell Proliferation / Clone Cells / Dendritic Cells / Epitopes / Graft Survival / Immune Tolerance / Injections / Membrane Proteins / Mice / Side-Population Cells / Skin Transplantation / T-Lymphocytes / Thymus Gland / Time Factors / Transplantation, Homologous (Link to Publication Site) ● Publication site (DOI): 10.1182/blood-2010-07-293860 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21220748 ● Search Scopus @ Elsevier (PMID): 21220748 ● Search Scopus @ Elsevier (DOI): 10.1182/blood-2010-07-293860 (DOI: 10.1182/blood-2010-07-293860, PubMed: 21220748)
79.	Yu Lei, Adiratna Mat Ripen, Naozumi Ishimaru, Izumi Ohigashi, Takashi Nagasawa, Lukas T. Jeker, Michael R. Bösl, Georg A. Holländer, Yoshio Hayashi, Rene Waal de Malefyt, Takeshi Nitta and Yousuke Takahama : Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development, The Journal of Experimental Medicine, Vol.208, No.2, 383-394, 2011. (Summary) Dendritic cells (DCs) in the thymus (tDCs) are predominantly accumulated in the medulla and contribute to the establishment of self-tolerance. However, how the medullary accumulation of tDCs is regulated and involved in self-tolerance is unclear. We show that the chemokine receptor XCR1 is expressed by tDCs, whereas medullary thymic epithelial cells (mTECs) express the ligand XCL1. XCL1-deficient mice are defective in the medullary accumulation of tDCs and the thymic generation of naturally occurring regulatory T cells (nT reg cells). Thymocytes from XCL1-deficient mice elicit dacryoadenitis in nude mice. mTEC expression of XCL1, tDC medullary accumulation, and nT reg cell generation are diminished in Aire-deficient mice. These results indicate that the XCL1-mediated medullary accumulation of tDCs contributes to nT reg cell development and is regulated by Aire. (Keyword) Animals / Chemokines / Chemokines, C / Chemotaxis / Dacryocystitis / Dendritic Cells / Flow Cytometry / Fluorescent Antibody Technique / Image Processing, Computer-Assisted / Mice / Mice, Nude / Microscopy, Confocal / Reverse Transcriptase Polymerase Chain Reaction / Self Tolerance / T-Lymphocytes, Regulatory / Thymus Gland / Transcription Factors (Link to Publication Site) ● Publication site (DOI): 10.1084/jem.20102327 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21300913 ● Search Scopus @ Elsevier (PMID): 21300913 ● Search Scopus @ Elsevier (DOI): 10.1084/jem.20102327 (DOI: 10.1084/jem.20102327, PubMed: 21300913)
80.	Emi Kawakami, Nao Kinouchi, Taro Adachi, Yutaka Ohsawa, Naozumi Ishimaru, Hideyo Ohuchi, Yoshihide Sunada, Yoshio Hayashi, Eiji Tanaka and Sumihare Noji : Atelocollagen-mediated systemic administration of myostatin-targeting siRNA improves muscular atrophy in caveolin-3-deficient mice., Development Growth & Differentiation, Vol.53, No.1, 48-54, 2011. (Summary) Small interfering RNA (siRNA)-mediated silencing of gene expression is rapidly becoming a powerful tool for molecular therapy. However, the rapid degradation of siRNAs and their limited duration of activity require efficient delivery methods. Atelocollagen (ATCOL)-mediated administration of siRNAs is a promising approach to disease treatment, including muscular atrophy. Herein, we report that ATCOL-mediated systemic administration of a myostatin-targeting siRNA into a caveolin-3-deficient mouse model of limb-girdle muscular dystrophy 1C (LGMD1C) induced a marked increase in muscle mass and a significant recovery of contractile force. These results provide evidence that ATCOL-mediated systemic administration of siRNAs may be a powerful therapeutic tool for disease treatment, including muscular atrophy. (Keyword) Animals / Caveolin 3 / Collagen / Female / Male / Mice / Muscular Atrophy / Myostatin / RNA Interference / RNA, Small Interfering (Link to Publication Site) ● Publication site (DOI): 10.1111/j.1440-169X.2010.01221.x (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21261610 ● Search Scopus @ Elsevier (PMID): 21261610 ● Search Scopus @ Elsevier (DOI): 10.1111/j.1440-169X.2010.01221.x (DOI: 10.1111/j.1440-169X.2010.01221.x, PubMed: 21261610)
81.	Taro Adachi, Emi Kawakami, Naozumi Ishimaru, Takahiro Ochiya, Yoshio Hayashi, Hideyo Ohuchi, Masao Tanihara, Eiji Tanaka and Sumihare Noji : Delivery of small interfering RNA with a synthetic collagen poly(Pro-Hyp-Gly) for gene silencing in vitro and in vivo., Development Growth & Differentiation, Vol.52, No.8, 693-699, 2010. (Summary) Silencing gene expression by small interfering RNAs (siRNAs) has become a powerful tool for the genetic analysis of many animals. However, the rapid degradation of siRNA and the limited duration of its action in vivo have called for an efficient delivery technology. Here, we describe that siRNA complexed with a synthetic collagen poly(Pro-Hyp-Gly) (SYCOL) is resistant to nucleases and is efficiently transferred into cells in vitro and in vivo, thereby allowing long-term gene silencing in vivo. We found that the SYCOL-mediated local application of siRNA targeting myostatin, coding a negative regulator of skeletal muscle growth, in mouse skeletal muscles, caused a marked increase in the muscle mass within a few weeks after application. Furthermore, in vivo administration of an anti-luciferase siRNA/SYCOL complex partially reduced luciferase expression in xenografted tumors in vivo. These results indicate a SYCOL-based non-viral delivery method could be a reliable simple approach to knockdown gene expression by RNAi in vivo as well as in vitro. (Keyword) Animals / Base Sequence / Cell Line, Tumor / Collagen / DNA Primers / Gene Silencing / Mice / RNA, Small Interfering / Reverse Transcriptase Polymerase Chain Reaction (Link to Publication Site) ● Publication site (DOI): 10.1111/j.1440-169X.2010.01206.x (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20874713 ● Search Scopus @ Elsevier (PMID): 20874713 ● Search Scopus @ Elsevier (DOI): 10.1111/j.1440-169X.2010.01206.x (DOI: 10.1111/j.1440-169X.2010.01206.x, PubMed: 20874713)
82.	Takashi Sakai, Li Liu, Xichuan Teng, Naozumi Ishimaru, Rika Mukai-Sakai, HoangNam Tran, Sun Mi Kim, Nobuya Sano, Yoshio Hayashi, Ryuji Kaji and Kiyoshi Fukui : Inflammatory disease and cancer with a decrease in Kupffer cell numbers in Nucling-knockout mice., International Journal of Cancer, Vol.126, No.5, 1079-1094, 2010. (Summary) Nucling is a stress-inducible protein associated with apoptosomes. The cytochrome c-triggered formation of apoptosomes represents a key-initiating event in apoptosis. We have recently reported that Nucling regulates the apoptotic pathway by controlling the activation of NF-kappaB as well. Here we show that hepatocellular carcinoma (HCC) arising spontaneously against a background of hepatitis occurred more frequently in Nucling-knockout (KO) mice than wild-type (WT) mice. Biochemical serum testing revealed potential liver dysfunction with hypercholesterolemia in Nucling-KO males. In the background of Nucling-KO mice, we observed the up-regulation of TNFalpha, spontaneous NF-kappaB-activation and the induction of galectin-3 expression in liver. In addition, we observed a decrease in the number of Kupffer cells (KCs) in the KO mice. KCs are important for the hepatic immune system, acting as phagocytes or antigen-presenting cells (APCs). We found that KCs in Nucling-KO mice were apoptotic possibly through the up-regulation of TNFalpha. These observations indicate that Nucling is important for the regulation of NF-kappaB signals in liver. We propose that Nucling deficiency could be a powerful tool to reveal the NF-kappaB-related molecular networks leading to hepatitis and HCC development. (Keyword) Animals / apoptosis / Blotting, Western / carbon tetrachloride / Carcinogens / Carcinoma, Hepatocellular / Electrophoretic Mobility Shift Assay / Flow Cytometry / Hepatitis / immunohistochemistry / inflammation / Kupffer Cells / Liver Neoplasms / Membrane Proteins / Mice / knockout mice / NF-kappa B / Precancerous Conditions / Reverse Transcriptase Polymerase Chain Reaction / Signal Transduction / Tumor Necrosis Factor-alpha (Link to Publication Site) ● Publication site (DOI): 10.1002/ijc.24789 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19637241 ● Summary page in Scopus @ Elsevier: 2-s2.0-74049095937 (DOI: 10.1002/ijc.24789, PubMed: 19637241, Elsevier: Scopus)
83.	Seiko Tatehara, Kenji Fujisawa, Hirokazu Nagai, Shuji Shigemoto, Kazuo Okura, Naozumi Ishimaru, Yoshio Hayashi and Youji Miyamoto : 切除からインプラントを維持源としたエピテーゼまで一貫治療を行った上顎洞悪性線維性組織球腫の1例, Shikoku Dental Research, Vol.22, No.2, 179-183, 2010. (Tokushima University Institutional Repository) ● Metadata: 109796 (Tokushima University Institutional Repository: 109796)
84.	Naozumi Ishimaru, 小橋真之, Akiko Yamada, Rieko Arakaki and Yoshio Hayashi : 新生児におけるダイオキシンへの曝露と自己免疫病の発生, Clinical Immunology & Allergology, Vol.53, No.1, 92-96, 2010. (Keyword) dioxin / autoimmunity / Sjögren`s syndrome / T cell ,Ahr (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1523951030120114944 (CiNii: 1523951030120114944)
85.	Naozumi Ishimaru, Takeshi Nitta, Rieko Arakaki, Akiko Yamada, Martin Lipp, Yousuke Takahama and Yoshio Hayashi : In situ Patrolling of Regulatory T cells is Essential for Protecting Autoimmune Exocrinopathy, PLoS ONE, Vol.5, No.1, e8588, 2010. (Summary) Migration of T cells, including regulatory T (Treg) cells, into the secondary lymph organs is critically controlled by chemokines and adhesion molecules. However, the mechanisms by which Treg cells regulate organ-specific autoimmunity via these molecules remain unclear. Although we previously reported autoimmune exocrinopathy resembling Sjögren's syndrome (SS) in the lacrimal and salivary glands from C-C chemokine receptor 7 (CCR7)-deficient mice, it is still unclear whether CCR7 signaling might specifically affect the dynamics and functions of Treg cells in vivo. We therefore investigated the cellular mechanism for suppressive function of Treg cells via CCR7 in autoimmunity using mouse models and human samples. Patrolling Treg cells were detected in the exocrine organs such as lacrimal and salivary glands from normal mice that tend to be targets for autoimmunity while the Treg cells were almost undetectable in the exocrine glands of CCR7(-/-) mice. In addition, we found the significantly increased retention of CD4(+)CD25(+)Foxp3(+) Treg cells in the lymph nodes of CCR7(-/-) mice with aging. Although Treg cell egress requires sphingosine 1-phosphate (S1P), chemotactic function to S1P of CCR7-/- Treg cells was impaired compared with that of WT Treg cells. Moreover, the in vivo suppression activity was remarkably diminished in CCR7(-/-) Treg cells in the model where Treg cells were co-transferred with CCR7(-/-) CD25(-)CD4(+) T cells into Rag2(-/-) mice. Finally, confocal analysis showed that CCR7(+)Treg cells were detectable in normal salivary glands while the number of CCR7(+)Treg cells was extremely decreased in the tissues from patients with Sjögren's syndrome. These results indicate that CCR7 essentially governs the patrolling functions of Treg cells by controlling the traffic to the exocrine organs for protecting autoimmunity. Characterization of this cellular mechanism could have clinical implications by supporting development of new diagnosis or treatments for the organ-specific autoimmune diseases such as Sjögren's syndrome and clarifying how the local immune system regulates autoimmunity. (Keyword) Animals / Autoimmune Diseases / Cell Movement / Exocrine Glands / Lymphoid Tissue / Mice / Mice, Knockout / Receptors, CCR7 / T-Lymphocytes, Regulatory (Link to Publication Site) ● Publication site (DOI): 10.1371/journal.pone.0008588 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20052419 ● Search Scopus @ Elsevier (PMID): 20052419 ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0008588 (DOI: 10.1371/journal.pone.0008588, PubMed: 20052419)
86.	Akiko Yamada, Naozumi Ishimaru, Rieko Arakaki, Nobuhiko Katsunuma and Yoshio Hayashi : Cathepsin L inhivition prevents murine autoimmune diabetes via suppression of CD⁸⁺ T cell activity., PLoS ONE, Vol.5, No.9, e12894, 2010. (Summary) Type 1 diabetes (T1D) is an autoimmune disease resulting from defects in central and peripheral tolerance and characterized by T cell-mediated destruction of islet β cells. To determine whether specific lysosomal proteases might influence the outcome of a T cell-mediated autoimmune response, we examined the functional significance of cathepsin inhibition on autoimmune T1D-prone non-obese diabetic (NOD) mice. Here it was found that specific inhibition of cathepsin L affords strong protection from cyclophosphamide (CY)-induced insulitis and diabetes of NOD mice at the advanced stage of CD8(+) T cell infiltration via inhibiting granzyme activity. It was discovered that cathepsin L inhibition prevents cytotoxic activity of CD8(+) T cells in the pancreatic islets through controlling dipeptidyl peptidase I activity. Moreover, the gene targeting for cathepsin L with application of in vivo siRNA administration successfully prevented CY-induced diabetes of NOD mice. Finally, cathepsin L mRNA expression of peripheral CD8(+) T cells from NOD mice developing spontaneous T1D was significantly increased compared with that from control mice. Our results identified a novel function of cathepsin L as an enzyme whose activity is essential for the progression of CD8(+) T cell-mediated autoimmune diabetes, and inhibition of cathepsin L as a powerful therapeutic strategy for autoimmune diabetes. (Keyword) Animals / Autoimmunity / CD8-Positive T-Lymphocytes / Cathepsin L / Diabetes Mellitus, Type 1 / Disease Models, Animal / Down-Regulation / Female / Humans / Mice / Mice, Inbred NOD (Link to Publication Site) ● Publication site (DOI): 10.1371/journal.pone.0012894 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20877570 ● Search Scopus @ Elsevier (PMID): 20877570 ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0012894 (DOI: 10.1371/journal.pone.0012894, PubMed: 20877570)
87.	Takeshi Nitta, Shigeo Murata, Katsuhiro Sasaki, Hideki Fujii, Adiratna Mat Ripen, Naozumi Ishimaru, Shigeo Koyasu, Keiji Tanaka and Yousuke Takahama : Thymoproteasome shapes immunocompetent repertoire of CD8⁺ T cells., Immunity, Vol.32, No.1, 29-40, 2010. (Summary) How self-peptides displayed in the thymus contribute to the development of immunocompetent and self-protective T cells is largely unknown. In contrast, the role of thymic self-peptides in eliminating self-reactive T cells and thereby preventing autoimmunity is well established. A type of proteasome, termed thymoproteasome, is specifically expressed by thymic cortical epithelial cells (cTECs) and is required for the generation of optimal cellularity of CD8+ T cells. Here, we show that cTECs displayed thymoproteasome-specific peptide-MHC class I complexes essential for the positive selection of major and diverse repertoire of MHC class I-restricted T cells. CD8+ T cells generated in the absence of thymoproteasomes displayed a markedly altered T cell receptor repertoire that was defective in both allogeneic and antiviral responses. These results demonstrate that thymoproteasome-dependent self-peptide production is required for the development of an immunocompetent repertoire of CD8+ T cells. (Keyword) Animals / CD8-Positive T-Lymphocytes / cell differentiation / Epithelial Cells / Histocompatibility Antigens Class I / Lymphocyte Activation / Mice / Mice, Knockout / Proteasome Endopeptidase Complex / Self Tolerance / T-Lymphocyte Subsets / Thymus Gland (Link to Publication Site) ● Publication site (DOI): 10.1016/j.immuni.2009.10.009 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20045355 ● Search Scopus @ Elsevier (PMID): 20045355 ● Search Scopus @ Elsevier (DOI): 10.1016/j.immuni.2009.10.009 (DOI: 10.1016/j.immuni.2009.10.009, PubMed: 20045355)
88.	Yoshio Hayashi, Rieko Arakaki and Naozumi Ishimaru : Salivary gland and autoimmunity, The Journal of Medical Investigation : JMI, Vol.56, 185-191, 2009. (Summary) Recent evidences suggest that the apoptotic pathway plays a central role in tolerazing T cells to tissue-specific self antigen, and may drive the autoimmune phenomenon in the salivary glands. We found that retinoblastoma-associated protein RbAp48 overexpression induces p53-mediated apoptosis in the salivary glands caused by estrogen deficiency. We demonstrated that transgenic (Tg) expression of RbAp48 resulted in the development of autoimmune exocrinopathy resembling Sjögren's syndrome (SS). CD4(+)T cell-mediated autoimmune lesions in the salivary glands were aggravated with age, in association with autoantibody productions. We obtained evidences that salivary epithelial cells can produce interferon-gamma (IFN-gamma) besides interleukin (IL)-18, which activates interferon regulatory factor-1 (IRF-1), and class II transactivator (CIITA). Indeed, the autoimmune lesions into Rag2(-/-) mice were induced by the adoptive transfer of lymph node cells from RbAp48-Tg mice. These results indicate a novel immunocompetent role of epithelial cells that can produce IFN-gamma, resulting in loss of local tolerance prior to developing gender-based autoimmunity. The studies reviewed the molecular mechanisms on the development of salivary gland autoimmunity, and gender-related differences in SS. (Keyword) Animals / Apoptosis / Autoimmunity / Disease Models, Animal / Female / Male / Mice / Mice, Transgenic / Retinoblastoma-Binding Protein 4 / Salivary Glands / Sex Characteristics / Sjogren's Syndrome / T-Lymphocytes (Tokushima University Institutional Repository) ● Metadata: 111327 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.56.185 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20224179 ● Search Scopus @ Elsevier (PMID): 20224179 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.56.185 (Tokushima University Institutional Repository: 111327, DOI: 10.2152/jmi.56.185, PubMed: 20224179)
89.	Yoshio Hayashi, Naozumi Ishimaru and Rieko Arakaki : シェーグレン症候群, 感染・炎症・免疫, Vol.39, No.3, 252-254, 2009.
90.	Naozumi Ishimaru and Yoshio Hayashi : Sjögren症候群の発症とエストロゲン, Clinical Immunology, Vol.52, No.4, 431-437, 2009.
91.	Kimi Yamakoshi, Akiko Takahashi, Fumiko Hirota, Rika Nakayama, Naozumi Ishimaru, Yoshiaki Kubo, J. David Mann, Masako Ohmura, Atsushi Hirao, Hideyuki Saya, Seiji Arase, Yoshio Hayashi, Kazuki Nakao, Mitsuru Matsumoto, Naoko Ohtani and Eiji Hara : Real-time in vivo imaging of p16Ink4a reveals cross-talk with p53, The Journal of Cell Biology, Vol.186, No.3, 393-407, 2009. (Summary) Expression of the p16(Ink4a) tumor suppressor gene, a sensor of oncogenic stress, is up-regulated by a variety of potentially oncogenic stimuli in cultured primary cells. However, because p16(Ink4a) expression is also induced by tissue culture stress, physiological mechanisms regulating p16(Ink4a) expression remain unclear. To eliminate any potential problems arising from tissue culture-imposed stress, we used bioluminescence imaging for noninvasive and real-time analysis of p16(Ink4a) expression under various physiological conditions in living mice. In this study, we show that oncogenic insults such as ras activation provoke epigenetic derepression of p16(Ink4a) expression through reduction of DNMT1 (DNA methyl transferase 1) levels as a DNA damage response in vivo. This pathway is accelerated in the absence of p53, indicating that p53 normally holds the p16(Ink4a) response in check. These results unveil a backup tumor suppressor role for p16(Ink4a) in the event of p53 inactivation, expanding our understanding of how p16(Ink4a) expression is regulated in vivo. (Keyword) Animals / Cells, Cultured / Cyclin-Dependent Kinase Inhibitor p16 / Disease Models, Animal / Gene Expression Profiling / Humans / Mice / Mice, Inbred C57BL / Mice, Knockout / Mice, Transgenic / Reverse Transcriptase Polymerase Chain Reaction / Time Factors / Tumor Suppressor Protein p53 (Link to Publication Site) ● Publication site (DOI): 10.1083/jcb.200904105 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19667129 ● Search Scopus @ Elsevier (PMID): 19667129 ● Search Scopus @ Elsevier (DOI): 10.1083/jcb.200904105 (DOI: 10.1083/jcb.200904105, PubMed: 19667129)
92.	Takeo Iwata, Masamichi Kuwajima, Akiko Sukeno, Naozumi Ishimaru, Yoshio Hayashi, Martin Wabitsch, Noriko Mizusawa, Mitsuo Itakura and Katsuhiko Yoshimoto : YKL-40 secreted from adipose tissue inhibits degradation of type I collagen., Biochemical and Biophysical Research Communications, Vol.388, No.3, 511-516, 2009. (Summary) Obesity is considered a chronic low-grade inflammatory status and the stromal vascular fraction (SVF) cells of adipose tissue (AT) are considered a source of inflammation-related molecules. We identified YKL-40 as a major protein secreted from SVF cells in human visceral AT. YKL-40 expression levels in SVF cells from visceral AT were higher than in those from subcutaneous AT. Immunofluorescence staining revealed that YKL-40 was exclusively expressed in macrophages among SVF cells. YKL-40 purified from SVF cells inhibited the degradation of type I collagen, a major extracellular matrix of AT, by matrix metalloproteinase (MMP)-1 and increased rate of fibril formation of type I collagen. The expression of MMP-1 in preadipocytes and macrophages was enhanced by interaction between these cells. These results suggest that macrophage/preadipocyte interaction enhances degradation of type I collagen in AT, meanwhile, YKL-40 secreted from macrophages infiltrating into AT inhibits the type I collagen degradation. (Keyword) Adipocytes / Adipose Tissue / Adult / Aged / Cells, Cultured / Coculture Techniques / Collagen Type I / Female / Glycoproteins / Humans / Inflammation / Lectins / Macrophages / Male / Matrix Metalloproteinase 1 / Middle Aged / Obesity / Stromal Cells (Tokushima University Institutional Repository) ● Metadata: 109641 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2009.08.024 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19666003 ● Search Scopus @ Elsevier (PMID): 19666003 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2009.08.024 (Tokushima University Institutional Repository: 109641, DOI: 10.1016/j.bbrc.2009.08.024, PubMed: 19666003)
93.	Naozumi Ishimaru, Takagi Atuya, Kohashi Masayuki, Akiko Yamada, Rieko Arakaki, Kanno Jun and Yoshio Hayashi : Neonatal Exposure to Loe-Dose 2.3.7.8-Tetrachlorodibenzo-p-Dioxin Causes Autoimmunity Due to the Disruption of TCell Tolerance1, The Journal of Immunology, Vol.182, No.10, 6576-6586, 2009. (Summary) Although 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to influence immune responses, the effects of low-dose TCDD on the development of autoimmunity are unclear. In this study, using NFS/sld mice as a model for human Sjögren's syndrome, in which the lesions are induced by the thymectomy on day 3 after birth, the autoimmune lesions in the salivary glands, and in later phase, inflammatory cell infiltrations in the other organs were developed by neonatal exposure to nonapoptotic dosage of TCDD without thymectomy on day 3 after birth. We found disruption of thymic selection, but not thymic atrophy, in TCDD-administered mice. The endogenous expression of aryl hydrocarbon receptor in the neonatal thymus was significantly higher than that in the adult thymus, suggesting that the neonatal thymus may be much more sensitive to TCDD compared with the adult thymus. In addition, the production of T(H)1 cytokines such as IL-2 and IFN-gamma from splenic CD4(+) T cells and the autoantibodies relevant for Sjögren's syndrome in the sera from TCDD-exposed mice were significantly increased compared with those in control mice. These results suggest that TCDD/aryl hydrocarbon receptor signaling in the neonatal thymus plays an important role in the early thymic differentiation related to autoimmunity. (Keyword) Animals / Animals, Newborn / Autoantigens / autoimmunity / Cell Proliferation / cytokinesis / Disease Models, Animal / Environmental pollutants / Enzyme-Linked Immunosorbent Assay / Flow Cytometry / Immune Tolerance / Mice / Mice, Mutant Strains / Microscopy, Confocal / Receptors, Aryl Hydrocarbon / Reverse Transcriptase Polymerase Chain Reaction / signal transduction / Sjögren's syndrome / T lymphocytes / Tetrachlorodibenzodioxin / Thymus Gland (Link to Publication Site) ● Publication site (DOI): 10.4049/jimmunol.0802289 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19414813 ● Search Scopus @ Elsevier (PMID): 19414813 ● Search Scopus @ Elsevier (DOI): 10.4049/jimmunol.0802289 (DOI: 10.4049/jimmunol.0802289, PubMed: 19414813)
94.	Rieko Arakaki, Ai Nagaoka, Naozumi Ishimaru, Akiko Yamada, Y Satoko and Yoshio Hayashi : Role of Plasmacytoid Dendric Cells for Aberrant Class Expression in Exocrine Glands from Estrogen-Deficient Mice of healthy Background, The American Journal of Pathology, Vol.174, No.5, 1715-1724, 2009. (Summary) Although it has been well documented that aberrant major histocompatibility complex class II molecules may contribute to the development of autoimmune disorders, the precise mechanisms responsible for their tissue-specific expression remain unknown. Here we show that estrogen deficiency induces aberrant class II major histocompatibility complex expression in exocrine glands via interactions between epithelial cells and plasmacytoid dendritic cells. Relatively modest but functionally significant expression levels of major histocompatibility complex class II and class II transactivator molecules were observed in the exocrine glands of ovariectomized (Ovx) C57BL/6 (B6) mice, but were not seen in the exocrine glands of control B6 mice. We observed that the salivary dendritic cells adjacent to the apoptotic epithelial cells positive for terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, were activated in Ovx mice, but were not activated in control mice. We obtained evidence that the salivary gland cells express both interferon regulatory factor-1 and class II transactivator type IV molecules in Ovx mice. Salivary gland cells from Ovx mice were also capable of inducing the activation of antigen-specific T cells from OT-II transgenic mice. These findings indicate that estrogen deficiency initiates class II transactivator type IV mRNA expression in exocrine glands via interactions between epithelial cells and plasmacytoid dendritic cells, suggesting that plasmacytoid dendritic cells play a pivotal role in gender-based autoimmune disorders in postmenopausal women. (Keyword) Animals / Antigen-Presenting Cells / Cell Proliferation / Cells, Cultured / Dendritic Cells / Enzyme-Linked Immunosorbent Assay / Epithelial Cells / Estrogens / Female / Flow Cytometry / Histocompatibility Antigens Class II / In Situ Nick-End Labeling / Interferon Regulatory Factor-1 / Interferon-gamma / Mice / Mice, Inbred C57BL / Mice, Transgenic / Nuclear Proteins / Ovariectomy / RNA, Messenger / Reverse Transcriptase Polymerase Chain Reaction / Salivary Glands / T-Lymphocytes / Trans-Activators (Link to Publication Site) ● Publication site (DOI): 10.2353/ajpath.2009.080695 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19359524 ● Search Scopus @ Elsevier (PMID): 19359524 ● Search Scopus @ Elsevier (DOI): 10.2353/ajpath.2009.080695 (DOI: 10.2353/ajpath.2009.080695, PubMed: 19359524)
95.	Naozumi Ishimaru, Rieko Arakaki, Satoko Yoshida, Akiko Yamada, Sumihare Noji and Yoshio Hayashi : Expression of the retinoblastoma protein RbAp48 in exocrine glands leads to Sjögren's syndrome-like autoimmune exocrinopathy., The Journal of Experimental Medicine, Vol.205, No.12, 2915-2927, 2008. (Summary) Although several autoimmune diseases are known to develop in postmenopausal women, the mechanisms by which estrogen deficiency influences autoimmunity remain unclear. Recently, we found that retinoblastoma-associated protein 48 (RbAp48) induces tissue-specific apoptosis in the exocrine glands depending on the level of estrogen deficiency. In this study, we report that transgenic (Tg) expression of RbAp48 resulted in the development of autoimmune exocrinopathy resembling Sjögren's syndrome. CD4(+) T cell-mediated autoimmune lesions were aggravated with age, in association with autoantibody productions. Surprisingly, we obtained evidence that salivary and lacrimal epithelial cells can produce interferon-gamma (IFN-gamma) in addition to interleukin-18, which activates IFN regulatory factor-1 and class II transactivator. Indeed, autoimmune lesions in Rag2(-/-) mice were induced by the adoptive transfer of lymph node T cells from RbAp48-Tg mice. These results indicate a novel immunocompetent role of epithelial cells that can produce IFN-gamma, resulting in loss of local tolerance before developing gender-based autoimmunity. (Keyword) Adoptive Transfer / Animals / Autoimmune Diseases / Biological Markers / Carrier Proteins / Cells, Cultured / Cytokines / DNA-Binding Proteins / Disease Models, Animal / Epithelial Cells / Exocrine Glands / Female / Genes, MHC Class II / Humans / Interferon-gamma / Interleukin-18 / Mice / Mice, Inbred C57BL / Mice, Transgenic / Nuclear Proteins / Retinoblastoma-Binding Protein 4 / Sjogren's Syndrome / T-Lymphocyte Subsets / T-Lymphocytes (Link to Publication Site) ● Publication site (DOI): 10.1084/jem.20080174 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19015307 ● Search Scopus @ Elsevier (PMID): 19015307 ● Search Scopus @ Elsevier (DOI): 10.1084/jem.20080174 (DOI: 10.1084/jem.20080174, PubMed: 19015307)
96.	Yu Hikosaka, Takeshi Nitta, Izumi Ohigashi, Kouta Yano, Naozumi Ishimaru, Yoshio Hayashi, Mitsuru Matsumoto, Koichi Matsuo, Josef M Penninger, Hiroshi Takayanagi, Yoshifumi Yokota, Hisakata Yamada, Yasunobu Yoshikai, Jun-ichiro Inoue, Taishin Akiyama and Yousuke Takahama : The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator., Immunity, Vol.29, No.3, 438-450, 2008. (Summary) The thymic medulla provides a microenvironment where medullary thymic epithelial cells (mTECs) express autoimmune regulator and diverse tissue-restricted genes, contributing to launching self-tolerance. Positive selection is essential for thymic medulla formation via a previously unknown mechanism. Here we show that the cytokine RANK ligand (RANKL) was produced by positively selected thymocytes and regulated the cellularity of mTEC by interacting with RANK and osteoprotegerin. Forced expression of RANKL restored thymic medulla in mice lacking positive selection, whereas RANKL perturbation impaired medulla formation. These results indicate that RANKL produced by positively selected thymocytes is responsible for fostering thymic medulla formation, thereby establishing central tolerance. (Keyword) Animals / Autoimmunity / Epithelial Cells / Mice / Osteoprotegerin / RANK Ligand / Receptor Activator of Nuclear Factor-kappa B / Receptors, Antigen, T-Cell / Self Tolerance / T-Lymphocytes / TNF-Related Apoptosis-Inducing Ligand / Thymus Gland / Transcription Factors (Link to Publication Site) ● Publication site (DOI): 10.1016/j.immuni.2008.06.018 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18799150 ● Search Scopus @ Elsevier (PMID): 18799150 ● Search Scopus @ Elsevier (DOI): 10.1016/j.immuni.2008.06.018 (DOI: 10.1016/j.immuni.2008.06.018, PubMed: 18799150)
97.	中野誠一, 山本元久, 嶽村貞治, Naozumi Ishimaru, Katsushi Miyazaki, Koichi Tamura, 氷見徹夫, Yoshio Hayashi and Noriaki Takeda : Three Cases of Mikulicz's Disease as an IgG4-related Disease, Practica Oto-Rhino-Laryngologica, Vol.101, No.8, 591-597, 2008. (Summary) We reported three cases of Mikuhcz's disease. Mikulicz's disease was diagnosed by the following criteria: 1) symmetrical enlargement of the lacrimal and salivary glands lasting at least 3 months', 2) the lacrimal and salivary glands were microscopically involved in the infiltration of inflammatory cells, 3) sarcoidosis and other lymphoproliferative diseases were excluded. Three patients with Mikulicz's disease were all characterized by elevated IgG4 concentration in the serum and prominent infiltration of IgG4-positive plasmacytes in the minor salivary glands. On the contrary, there were no findings indicating sicca syndrome or anti-SS-A and SS-B antibodies, which characterize Sjögren syndrome. It is suggested that Mikulicz's disease is an IgG4-related plasmacytec disease, with a pathogenesis differing from that of Sjögren syndrome. (Keyword) Mikulicz's disease / mikuliczs disease / IgG4 / igg4 / lacrimal gland / lacrimal gland / salivary gland / salivary gland / Sjogren syndrome / sjogren syndrome (Link to Publication Site) ● Publication site (DOI): 10.5631/jibirin.101.591 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390001204263350656 ● Summary page in Scopus @ Elsevier: 2-s2.0-49749097528 (DOI: 10.5631/jibirin.101.591, CiNii: 1390001204263350656, Elsevier: Scopus)
98.	Nao Kinouchi, Yutaka Ohsawa, Naozumi Ishimaru, Hideyo Ohuchi, Y Sunada, Yoshio Hayashi, Yukiho Tanimoto, Keiji Moriyama and Sumihare Noji : Atelocollagen-mediated local and systemic applications of myostatin-targeting siRNA increase skeletal muscle mass., Gene Therapy, Vol.15, No.15, 1126-1130, 2008. (Summary) RNA interference (RNAi) offers a novel therapeutic strategy based on the highly specific and efficient silencing of a target gene. Since it relies on small interfering RNAs (siRNAs), a major issue is the delivery of therapeutically active siRNAs into the target tissue/target cells in vivo. For safety reasons, strategies based on vector delivery may be of only limited clinical use. The more desirable approach is to directly apply active siRNAs in vivo. Here, we report the effectiveness of in vivo siRNA delivery into skeletal muscles of normal or diseased mice through nanoparticle formation of chemically unmodified siRNAs with atelocollagen (ATCOL). ATCOL-mediated local application of siRNA targeting myostatin, a negative regulator of skeletal muscle growth, in mouse skeletal muscles or intravenously, caused a marked increase in the muscle mass within a few weeks after application. These results imply that ATCOL-mediated application of siRNAs is a powerful tool for future therapeutic use for diseases including muscular atrophy. (Keyword) Animals / Collagen / Gene Therapy / Immunohistochemistry / Injections, Intramuscular / Injections, Intravenous / Male / Mice / Mice, Inbred mdx / Muscle, Skeletal / Muscular Dystrophy, Animal / Myostatin / Nanoparticles / RNA Interference / RNA, Small Interfering / Transforming Growth Factor beta (Link to Publication Site) ● Publication site (DOI): 10.1038/gt.2008.24 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18323791 ● Search Scopus @ Elsevier (PMID): 18323791 ● Search Scopus @ Elsevier (DOI): 10.1038/gt.2008.24 (DOI: 10.1038/gt.2008.24, PubMed: 18323791)
99.	Naozumi Ishimaru, Akiko Yamada, Masayuki Kohashi, Rieko Arakaki, Tetsuyuki Takahashi, Keisuke Izumi and Yoshio Hayashi : Development of Inflammatory Bowel Disease in Long-Evans Cinnamon Rats Based on CD4+CD25+Foxp3+ Regulatory T Cell Dysfunction, The Journal of Immunology, Vol.180, No.10, 6997-7008, 2008. (Summary) A mutant strain with defective thymic selection of the Long-Evans Cinnamon (LEC) rat was found to spontaneously develop inflammatory bowel disease (IBD)-like colitis. The secretion of Th1-type cytokines including IFN-gamma and IL-2 from T cells of mesenteric lymph node cells (MLNs) and lamina propria mononuclear cells, but not spleen cells, in LEC rats was significantly increased more than that of the control Long-Evans Agouti rats through up-regulated expression of T-bet and phosphorylation of STAT-1 leading to NF-kappaB activation. In addition, the number of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells of the thymus, MLNs, and lamina propria mononuclear cells from LEC rats was significantly reduced, comparing with that of the control rats. Moreover, bone marrow cell transfer from LEC rats into irradiated control rats revealed significantly reduced CD25(+)Foxp3(+) Treg cells in thymus, spleen, and MLNs compared with those from control rats. Indeed, adoptive transfer with T cells of MLNs, not spleen cells, from LEC rats into SCID mice resulted in the development of inflammatory lesions resembling the IBD-like lesions observed in LEC rats. These results indicate that the dysfunction of the regulatory system controlled by Treg cells may play a crucial role in the development of IBD-like lesions through up-regulated T-bet, STAT-1, and NF-kappaB activation of peripheral T cells in LEC rats. (Keyword) Adoptive Transfer / Animals / Blotting, Western / Cell Proliferation / Cytokines / Enzyme-Linked Immunosorbent Assay / Flow Cytometry / Fluorescent Antibody Technique / Forkhead Transcription Factors / Inflammatory Bowel Diseases / Lymph Nodes / Lymphocyte Activation / Mice / Mice, SCID / Microscopy, Confocal / NF-kappa B / Rats / Rats, Inbred LEC / Rats, Mutant Strains / Reverse Transcriptase Polymerase Chain Reaction / STAT1 Transcription Factor / Spleen / T-Box Domain Proteins / T-Lymphocytes, Regulatory / Thymus Gland (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18453622 ● Search Scopus @ Elsevier (PMID): 18453622 (PubMed: 18453622)
100.	Masayuki Kohashi, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : Effective Treatment With Oral Administration of Rebamipide in a Model of Sjogren's Syndrome, Arthritis and Rheumatism, Vol.58, No.2, 389-400, 2008. (Summary) To determine whether oral administration of rebamipide, a mucosal protective agent, is effective in the treatment of Sjögren's syndrome (SS) in the NFS/sld mouse model of the disease. NFS/sld mice were given daily oral doses of rebamipide (0.3 mg/kg of body weight or 3 mg/kg) or vehicle alone starting from the age of 4 weeks to the age of 8 weeks. The volume of saliva and tears was monitored during and after treatment. After the final dose, histologic features of the tissues, TUNEL+ apoptotic duct cells in affected glands, T cell and cytokine function, and levels of immunoglobulin isotypes and serum autoantibodies were examined. The 3-mg/kg dose of rebamipide prevented the development of autoimmune lesions. The average volume of saliva in rebamipide-treated mice was significantly higher than that in control mice. We found decreased TUNEL+ apoptotic duct cells in the salivary and lacrimal glands of rebamipide-treated mice as compared with control mice. Rebamipide treatment suppressed the activation of CD4+ T cells and Th1 cytokines (interleukin-2, interferon-gamma) associated with impaired NF-kappaB activity. Production of serum autoantibodies, IgM, and IgG1 was clearly inhibited. Our findings demonstrate the efficacy of oral administration of rebamipide in the treatment of SS. Rebamipide represents a new therapeutic strategy for the treatment of patients with sicca symptoms caused by SS, as well as for patients with other diseases. (Keyword) Administration, Oral / Alanine / Animals / Anti-Inflammatory Agents / Autoantibodies / Cell Division / Cytokines / Disease Models, Animal / Female / Immunologic Factors / Lacrimal Apparatus / Mice / Mice, Mutant Strains / Quinolones / Salivary Glands / Sjogren's Syndrome / T-Lymphocytes / Thymectomy (Link to Publication Site) ● Publication site (DOI): 10.1002/art.23163 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18240266 ● Search Scopus @ Elsevier (PMID): 18240266 ● Search Scopus @ Elsevier (DOI): 10.1002/art.23163 (DOI: 10.1002/art.23163, PubMed: 18240266)
101.	Kazuhito Satomura, Reiko Tokuyama, Tetsuya Yuasa, Y Yamasaki, Seiko Tatehara, Naozumi Ishimaru, Yoshio Hayashi and Masaru Nagayama : Possible involvement of stem cell factor and endothelin-1 in the emergence of pigmented squamous cell carcinoma in oral mucosa., Journal of Oral Pathology & Medicine, Vol.36, No.10, 621-624, 2007. (Summary) We present here the clinical, morphological and immunohistochemical features of a pigmented squamous cell carcinoma (SCC) in the oral mucosa of the hard palate of a 76-year-old Japanese man. He underwent a partial resection of the maxilla subsequent to radiotherapy. The tumor was typical, moderately well-differentiated SCC but had many melanocytes (melanocytosis) within it. Immunohistochemical analysis for stem cell factor (SCF) and endothelin-1, both of which are known to stimulate proliferation and differentiation of melanocytes, revealed prominent expression of both factors in the neoplastic squamous cells of the pigmented SCC, while the non-pigmented oral SCC showed little sign of either factor. These findings strongly suggest that SCF and endothelin-1 secreted by neoplasmic squamous cells are involved in the emergence of a rare variant of oral SCC. (Keyword) Aged / Carcinoma, Squamous Cell / Endothelin-1 / Humans / Male / Melanocytes / Melanosis / Palatal Neoplasms / Stem Cell Factor (Link to Publication Site) ● Publication site (DOI): 10.1111/j.1600-0714.2007.00587.x (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17944756 ● Search Scopus @ Elsevier (PMID): 17944756 ● Search Scopus @ Elsevier (DOI): 10.1111/j.1600-0714.2007.00587.x (DOI: 10.1111/j.1600-0714.2007.00587.x, PubMed: 17944756)
102.	Naoko Ohtani, Yuko Imamura, Kimi Yamakoshi, Fumiko Hirota, Rika Nakayama, Yoshiaki Kubo, Naozumi Ishimaru, Akiko Takahashi, Atsushi Hirao, Takatsune Shimizu, David J. Mann, Hideyuki Saya, Yoshio Hayashi, Seiji Arase, Mitsuru Matsumoto, Nakao Kazuki and Eiji Hara : Visualizing the dynamics of p21 (Wafl/Cip1)cyclin-dependent kinase inhibitor expression in living animals., Proceedings of the National Academy of Sciences of the United States of America, Vol.104, No.38, 15034-15039, 2007. (Summary) Although the role of p21(Waf1/Cip1) gene expression is well documented in various cell culture studies, its in vivo roles are poorly understood. To gain further insight into the role of p21(Waf1/Cip1) gene expression in vivo, we attempted to visualize the dynamics of p21(Waf1/Cip1) gene expression in living animals. In this study, we established a transgenic mice line (p21-p-luc) expressing the firefly luciferase under the control of the p21(Waf1/Cip1) gene promoter. In conjunction with a noninvasive bioluminescent imaging technique, p21-p-luc mice enabled us to monitor the endogenous p21(Waf1/Cip1) gene expression in vivo. By monitoring and quantifying the p21(Waf1/Cip1) gene expression repeatedly in the same mouse throughout its entire lifespan, we were able to unveil the dynamics of p21(Waf1/Cip1) gene expression in the aging process. We also applied this system to chemically induced skin carcinogenesis and found that the levels of p21(Waf1/Cip1) gene expression rise dramatically in benign skin papillomas, suggesting that p21(Waf1/Cip1) plays a preventative role(s) in skin tumor formation. Surprisingly, moreover, we found that the level of p21(Waf1/Cip1) expression strikingly increased in the hair bulb and oscillated with a 3-week period correlating with hair follicle cycle progression. Notably, this was accompanied by the expression of p63 but not p53. This approach, together with the analysis of p21(Waf1/Cip1) knockout mice, has uncovered a novel role for the p21(Waf1/Cip1) gene in hair development. These data illustrate the unique utility of bioluminescence imaging in advancing our understanding of the timing and, hence, likely roles of specific gene expression in higher eukaryotes. (Keyword) Animals / Cyclin-Dependent Kinase Inhibitor p21 / Firefly Luciferin / Fluorescent Antibody Technique / gene expression / Luciferases / Luminescent Agents / Luminescent Measurements / Mice / knockout mice / Mice, Transgenic / Reverse Transcriptase Polymerase Chain Reaction (Link to Publication Site) ● Publication site (DOI): 10.1073/pnas.0706949104 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17848507 ● Search Scopus @ Elsevier (PMID): 17848507 ● Search Scopus @ Elsevier (DOI): 10.1073/pnas.0706949104 (DOI: 10.1073/pnas.0706949104, PubMed: 17848507)
103.	Takashi Izawa, Naozumi Ishimaru, Keiji Moriyama, Masayuki Kohashi, Rieko Arakaki and Yoshio Hayashi : Crosstalk between RANKL and Fas signaling in dendritic cells controls immune tolerance, Blood, Vol.110, No.1, 242-250, 2007. (Summary) Although receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) signaling has been shown to prolong the survival of mature dendritic cells (DCs), the association of RANKL pathway with Fas-mediated apoptosis is obscure. Here, we found that bone marrow-derived DCs (BMDCs) from the Fas-deficient strain MRL/lpr mice, could survive much longer than normal DCs. The expressions of Bcl-x and Bcl-2 and the nuclear transport of NF-kappaB of RANKL-stimulated BMDCs from MRL/lpr mice were significantly up-regulated. By contrast, Fas expression of BMDCs from normal C57BL/6 and MRL(+/+) mice was increased by RANKL stimulation, and an enhanced DC apoptosis was found when stimulated with both RANKL and anti-Fas mAb, which was associated with activation of caspase-3 and caspase-9. Furthermore, the expression of FLIP(L), an inhibitory molecule against Fas-mediated apoptosis, in normal DCs was significantly decreased by RANKL and anti-Fas mAb. Indeed, the adoptive transfer of RANKL-stimulated DCs resulted in rapid acceleration of autoimmunity in MRL/lpr recipients. These findings indicate that the crosstalk between RANKL and Fas signaling in DCs might control immune tolerance. (Keyword) Animals / Antigens, CD95 / Apoptosis / Apoptosis Regulatory Proteins / Autoimmunity / Caspases / Dendritic Cells / Immune Tolerance / Mice / RANK Ligand / Receptor Cross-Talk / Signal Transduction / Up-Regulation (Link to Publication Site) ● Publication site (DOI): 10.1182/blood-2006-11-059980 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17371940 ● Search Scopus @ Elsevier (PMID): 17371940 ● Search Scopus @ Elsevier (DOI): 10.1182/blood-2006-11-059980 (DOI: 10.1182/blood-2006-11-059980, PubMed: 17371940)
104.	Naozumi Ishimaru, Hidehiro Kishimoto, Yoshio Hayashi and Jonathan Sprent : Regulation of naive T cell function by the NF-κB2 pathway, Nature Immunology, Vol.7, No.7, 763-772, 2006. (Summary) T cell activation involves the orchestration of several signaling pathways, including that of the 'classical' transcription factor NF-kappaB components NF-kappaB1-RelA. The function of the 'nonclassical' NF-kappaB2-RelB pathway is less clear, although T cells lacking components of this pathway have activation defects. Here we show that mice deficient in NF-kappaB-inducing kinase have a complex phenotype consisting of immunosuppression mediated by CD25(-)Foxp3(-) memory CD4(+) cells and, in the absence of those cells, hyper-responsive naive CD4(+) T cells, which caused autoimmune lesions after adoptive transfer into hosts deficient in recombination-activating genes. Biochemical studies indicated involvement of a cell-intrinsic mechanism in which NF-kappaB2 (p100) limits nuclear translocation of NF-kappaB1-RelA and thereby functions as a regulatory 'brake' for the activation of naive T cells. (Keyword) Active Transport, Cell Nucleus / Adoptive Transfer / Animals / Antigens, CD44 / Autoimmune Diseases / CD4-Positive T-Lymphocytes / Cells, Cultured / DNA-Binding Proteins / Forkhead Transcription Factors / Gene Expression Regulation / Immunologic Memory / Interleukin-2 / Lymphocyte Activation / Mice / Mice, Inbred Strains / NF-kappa B p50 Subunit / NF-kappa B p52 Subunit / Protein-Serine-Threonine Kinases / Transcription Factor RelA / Transcription Factor RelB (Link to Publication Site) ● Publication site (DOI): 10.1038/ni1351 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16732290 ● Search Scopus @ Elsevier (PMID): 16732290 ● Search Scopus @ Elsevier (DOI): 10.1038/ni1351 (DOI: 10.1038/ni1351, PubMed: 16732290)
105.	Nobuhiko Katunuma, Quang Trong Le, Etsuko Murata, Atsushi Matsui, Eiji Majima, Naozumi Ishimaru, Yoshio Hayashi and Atsushi Ohashi : A novel apoptosis cascade mediated by lysosomal lactoferrin and its participation in hepatocyte apoptosis induced by D-galactosamine., FEBS Letters, Vol.580, No.15, 3699-3705, 2006. (Summary) A new apoptosis cascade mediated by lysosomal lactoferrin was found in apoptotic liver induced by d-galactosamine. Caspase-3 and lactoferrin were increased in the apoptotic liver cytoplasm and serum transaminases were elevated. Recombinant lactoferrin stimulated procaspase-3 processing at 10(-6)-10(-7)M to an extent similar to that by granzyme B in vitro. Lactoferrin changed procaspase-3 structure susceptible to the processing. Synthetic peptide Y(679)-K(695) in lactoferrin molecule inhibited the processing of procaspase-3 by lactoferrin. Lactoferrin in lysosomes was decreased and lactoferrin released into cytoplasm was increased quantitatively in d-galactosamine induced apoptotic liver, and procaspase-3 in cytoplasm was processed to caspase-3. (Keyword) Animals / Apoptosis / Caspase 3 / Caspases / Enzyme Activation / Galactosamine / Hepatocytes / Lactoferrin / Lysosomes / Mice / Molecular Weight / Rats (Link to Publication Site) ● Publication site (DOI): 10.1016/j.febslet.2006.05.057 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16765951 ● Search Scopus @ Elsevier (PMID): 16765951 ● Search Scopus @ Elsevier (DOI): 10.1016/j.febslet.2006.05.057 (DOI: 10.1016/j.febslet.2006.05.057, PubMed: 16765951)
106.	Masayuki Azuma, Yuki Ashida, Tetsuya Tamatani, Katsumi Motegi, Natsumi Takamaru, Naozumi Ishimaru, Yoshio Hayashi and Mitsunobu Sato : Cepharanthin,a biscoclaurine alkaloid,prevents destruction of acinar tissues in murine Sjogren's syndrome., The Journal of Rheumatology, Vol.33, No.5, 912-920, 2006. (Summary) Our previous study suggested that suppression by cepharanthin of tumor necrosis factor-a (TNF-a)-induced matrix metalloproteinase-9 (MMP-9) could prevent destruction of the acinar structure in the salivary glands of patients with Sjögren's syndrome (SS). In this study, we observed that in vivo administration of cepharanthin prevented severe damage to acinar tissues in the murine model of human SS. Cepharanthin was intraperitoneally administered to thymectomized female NFS/sld mice. Inflammatory lesions in the salivary and lacrimal glands were then examined histologically. Expression of phosphorylated IkB-a, MMP-9, and type IV collagen was analyzed immunohistochemically. The apoptotic cell death of acinar cells was determined. Although extensive mononuclear cell infiltration and destruction of acinar tissue in salivary and lacrimal glands were observed in control mice, significant improvement of these lesions was evident in mice treated with cepharanthin. Immunohistochemical analysis revealed that p65, phosphorylated IkB-a, and MMP-9 were more strongly stained in the acinar cells of control mice than in cepharanthin-treated mice. Although no staining for type IV collagen was observed in the acinar tissues of control mice, continuity of staining for type IV collagen was observed in acinar tissues of cepharanthin-treated mice. Destruction of acinar tissues was attributed to the induction of apoptosis, suggesting that cepharanthin inhibits apoptosis by suppressing phosphorylation of IkB-a, followed by prevention of MMP-9 activation. Our findings suggest that cepharanthin may be a promising agent for use in preventing destruction of acinar tissues in murine SS. (Keyword) Alkaloids / Animals / Apoptosis / Benzylisoquinolines / Carrier Proteins / Collagen Type IV / Female / I-kappa B Proteins / Immunohistochemistry / Lacrimal Apparatus / Matrix Metalloproteinase 9 / Mice / Mice, Mutant Strains / Neoplasm Proteins / Salivary Glands / Sjogren's Syndrome / Transcription Factor RelA (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16652422 ● Search Scopus @ Elsevier (PMID): 16652422 (PubMed: 16652422)
107.	Naoto Suzue, Takeshi Nikawa, Yuko Onishi, Chiharu Yamada, Katsuya Hirasaka, Takayuki Ogawa, Harumi Furochi, Hirofumi Kosaka, Kazumi Ishidoh, Gu Hua, Shin'ichi Takeda, Naozumi Ishimaru, Yoshio Hayashi, Hironori Yamamoto, Kyoichi Kishi and Natsuo Yasui : Ubiqitin Ligase Cbl-b Downregulates Bone Formation Through Suppression of IGF-I Signaling in Osteoblasts During Denervation, Journal of Bone and Mineral Research, Vol.21, No.5, 722-734, 2006. (Summary) Unloading can prevent bone formation by osteoblasts. To study this mechanism, we focused on a ubiquitin ligase, Cbl-b, which was highly expressed in osteoblastic cells during denervation. Our results suggest that Cbl-b may mediate denervation-induced osteopenia by inhibiting IGF-I signaling in osteoblasts. Unloading, such as denervation (sciatic neurectomy) and spaceflight, suppresses bone formation by osteoblasts, leading to osteopenia. The resistance of osteoblasts to growth factors contributes to such unloading-mediated osteopenia. However, a detailed mechanism of this resistance is unknown. We first found that a RING-type ubiquitin ligase, Cbl-b, was highly expressed in osteoblastic cells after sciatic neurectomy in mice. In this study, we reasoned that Cbl-b played an important role in the resistance of osteoblasts to IGF-I. Cbl-b-deficient (Cbl-b(-/-)) or wildtype (Cbl-b(+/+)) mice were subjected to sciatic neurectomy. Bone formation in these mice was assessed by calcein labeling and histomorphometric analyses. We examined IGF-I signaling molecules in femora of these mice by Western blot and immunohistochemical analyses. We also examined the mitogenic response of Cbl-b-overexpressing or -deficient osteoblastic cells to various growth factors. In Cbl-b(+/+) mice, denervation decreased femur mass and bone formation, whereas it increased the expression of Cbl-b protein in osteoprogenitor cells and in osteocalcin-positive cells (osteoblastic cells) in hindlimb bone. In contrast, in Cbl-b(-/-) mice, bone mass and bone formation were sustained during denervation. Denervation inhibited the mitogenic response of osteoprogenitor cells most significantly to IGF-I. Therefore, we focused on Cbl-b-mediated modification of IGF-I signaling. Denervation decreased the amounts of insulin receptor substrate-1 (IRS-1), phosphatidly inositol 3-phosphate kinase (PI3K), and Akt-1 proteins in femora of Cbl-b(+/+) mice, whereas the amounts of these IGF-I signaling molecules in femora of Cbl-b(-/-) mice were constant after denervation. On a cellular level, primary osteoblastic cells from Cbl-b(-/-) mice were more stimulated to proliferate by IGF-I treatment compared with those from Cbl-b(+/+) mice. Furthermore, overexpression of Cbl-b increased ubiquitination and degradation of IRS-1 in primary Cbl-b(-/-) osteoblastic cells, leading to their impaired mitogenic response to IGF-I. These results suggest that Cbl-b induces resistance of osteoblasts to IGF-I during denervation by increasing IRS-1 degradation and that Cbl-b-mediated modification of IGF-I signaling may contribute to decreased bone formation during denervation. (Keyword) Animals / Base Sequence / Blotting, Western / Bone Development / Cells, Cultured / DNA Primers / Denervation / Down-Regulation / Hydrolysis / immunohistochemistry / Insulin-Like Growth Factor I / Mice / Mice, Inbred C57BL / Osteoblasts / Protein Binding / Reverse Transcriptase Polymerase Chain Reaction / signal transduction / Ubiquitin / Ubiquitin-Protein Ligases (Link to Publication Site) ● Publication site (DOI): 10.1359/jbmr.060207 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16734387 ● Summary page in Scopus @ Elsevier: 2-s2.0-33646227897 (DOI: 10.1359/jbmr.060207, PubMed: 16734387, Elsevier: Scopus)
108.	Naozumi Ishimaru, Rieko Arakaki, Fumie Omotehara, Kouichi Yamada, Kenji Mishima, Ichiro Saito and Yoshio Hayashi : Novel role for RbAp48 in tissue-specific,estrogen deficiency-dependent apoptosis in the exocrine glands., Molecular and Cellular Biology, Vol.26, No.8, 2924-2935, 2006. (Summary) Although tissue-specific apoptosis in the exocrine glands in estrogen-deficient mice may contribute to the development of autoimmune exocrinopathy, the molecular mechanism responsible for tissue-specific apoptosis remains obscure. Here we show that RbAp48 overexpression induces p53-mediated apoptosis in the exocrine glands caused by estrogen deficiency. RbAp48-inducible transfectant results in rapid apoptosis with p53 phosphorylation (Ser9) and alpha-fodrin cleavage. Reducing the expression of RbAp48 through small interfering RNA inhibits the apoptosis. Prominent RbAp48 expression with apoptosis was observed in the exocrine glands of C57BL/6 ovariectomized (OVX) mice but not in OVX estrogen receptor alpha(-/-), p53(-/-), and E2F-1(-/-) mice. Indeed, transgenic expression of the RbAp48 gene induced apoptosis in the exocrine glands but not in other organs. These findings indicate that estrogen deficiency initiates p53-mediated apoptosis in the exocrine gland cells through RbAp48 overexpression and exerts a possible gender-based risk of autoimmune exocrinopathy in postmenopausal women. (Keyword) Animals / Annexin A5 / Apoptosis / Blotting, Western / Carrier Proteins / Caspases / Cell Line, Tumor / Estrogen Receptor alpha / Female / Fluorescein-5-isothiocyanate / Fluorescent Dyes / HT29 Cells / HeLa Cells / Humans / Immunohistochemistry / Jurkat Cells / Mice / Mice, Inbred C57BL / Mice, Transgenic / Microfilament Proteins / Microscopy, Confocal / Nuclear Proteins / Organ Specificity / Ovariectomy / Phosphorylation / RNA, Small Interfering / Retinoblastoma-Binding Protein 4 / Salivary Glands / Tumor Suppressor Protein p53 / U937 Cells (Link to Publication Site) ● Publication site (DOI): 10.1128/MCB.26.8.2924-2935.2006 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16581768 ● Search Scopus @ Elsevier (PMID): 16581768 ● Search Scopus @ Elsevier (DOI): 10.1128/MCB.26.8.2924-2935.2006 (DOI: 10.1128/MCB.26.8.2924-2935.2006, PubMed: 16581768)
109.	Naozumi Ishimaru and Yoshio Hayashi : Crucial Roles of NF-kB for T Cell Activation, Journal of Oral Biosciences, Vol.48, No.1, 12-17, 2006. (Keyword) NF-κB / T cell activation / autoimmune disease / classical pathway / alternative pathway (Link to Publication Site) ● Publication site (DOI): 10.2330/joralbiosci.48.12 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390282680189358336 ● Search Scopus @ Elsevier (DOI): 10.2330/joralbiosci.48.12 (DOI: 10.2330/joralbiosci.48.12, CiNii: 1390282680189358336)
110.	Nobuhiko Katumuma, Atsushi Ohashi, Etsuko Sano, Naozumi Ishimaru, Yoshio Hayashi and Etsuko Murata : Catechin derivatives:specific inhibitor for caspases-3,7and 2,and the prevention of apoptosis at the cell and animal levels., FEBS Letters, Vol.580, No.3, 741-746, 2006. (Summary) Tea-catechin derivatives are shown to inhibit activities of caspases-3, 2 and 7 in vitro, and prevented experimental apoptosis at the cell and animal levels. Epigallo-catechin-gallate showed the strongest inhibition at 1 x 10(-7)M to these caspases, but cysteine cathepsins and caspase-8 were not inhibited. Caspase-3 inhibition showed a 2nd-order allosteric-type, but the inhibition of caspases-2 and 7 showed a non-competitive-type. The apoptosis-test using cultured HeLa cells was inhibited by these catechins. In rat hepatocytes, apoptosis was induced by d-galactosamine in vivo. In this case, caspase-3 activity in the cytoplasm, the serum aminotransferases and dUTP nick formation detected by TUNNEL-staining were effects, and these elevations were suppressed by administration of catechin. (Keyword) Animals / Apoptosis / Caspase 2 / Caspase 3 / Caspase 7 / Caspases / Catechin / Cell-Free System / Dose-Response Relationship, Drug / Enzyme Inhibitors / Galactosamine / HeLa Cells / Hepatocytes / Humans / In Situ Nick-End Labeling / Rats (Link to Publication Site) ● Publication site (DOI): 10.1016/j.febslet.2005.12.087 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16413020 ● Search Scopus @ Elsevier (PMID): 16413020 ● Search Scopus @ Elsevier (DOI): 10.1016/j.febslet.2005.12.087 (DOI: 10.1016/j.febslet.2005.12.087, PubMed: 16413020)
111.	Katsushi Miyazaki, Noriaki Takeda, Naozumi Ishimaru, Fumie Omotehara, Rieko Arakaki and Yoshio Hayashi : Analysis of in vivo role of alpha-fodrin autoantigen in primary Sjogren's syndrome, The American Journal of Pathology, Vol.167, No.4, 1051-1059, 2005. (Summary) The alpha-fodrin N-terminal portion (AFN) autoantigen mediates in vivo immunoregulation of autoimmune responses in primary Sjögren's syndrome (SS). We further examined this process and found that cleavage products of AFN were frequently detected in the salivary gland duct cells of SS patients. In in vitro studies using human salivary gland HSY cells, anti-Fas-induced apoptosis resulted in specific cleavage of alpha-fodrin into the 120-kd fragment, in association of alpha-fodrin with mu-calpain, and activation of caspase 3. Significant proliferative responses against AlphaFN autoantigen were observed in the peripheral blood mononuclear cells (PBMCs) from SS patients with higher pathological score (grade 4) and with short duration from onset (within 5 years). In vivo roles of AFN peptides were investigated using PBMCs from patients with SS, systemic lupus erythematosus, and rheumatoid arthritis. Significant proliferative T-cell responses of PBMCs to AFN peptide were detected in SS but not in systemic lupus erythematosus or rheumatoid arthritis. AFN peptide induced Th1-immune responses and accelerated down-regulation of Fas-mediated T-cell apoptosis in SS. Our data further elucidate the in vivo role of AFN autoantigen on the development of SS and suggest that the AFN autoantigen is a novel participant in peripheral tolerance. (Keyword) Amino Acid Sequence / Antibodies, Monoclonal / Antigens, CD95 / Apoptosis / Arthritis, Rheumatoid / Autoantigens / Blotting, Western / CD4-Positive T-Lymphocytes / CD8-Positive T-Lymphocytes / Calpain / Carrier Proteins / Case-Control Studies / Caspase 3 / Caspases / Cells, Cultured / Coculture Techniques / Enzyme Activation / Female / Furans / Glutathione Transferase / Humans / Immunohistochemistry / Japan / Leukocytes, Mononuclear / Lupus Erythematosus, Systemic / Microfilament Proteins / Molecular Sequence Data / Molecular Weight / Parotid Gland / Recombinant Fusion Proteins / Sjogren's Syndrome / Thymidine (Link to Publication Site) ● Publication site (DOI): 10.1016/S0002-9440(10)61194-7 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16192640 ● Search Scopus @ Elsevier (PMID): 16192640 ● Search Scopus @ Elsevier (DOI): 10.1016/S0002-9440(10)61194-7 (DOI: 10.1016/S0002-9440(10)61194-7, PubMed: 16192640)
112.	Noriyuki Kuroda, Tasuku Mitani, Naoki Takeda, Naozumi Ishimaru, Rieko Arakaki, Yoshio Hayashi, Yoshimi Bando, Keisuke Izumi, Takeshi Takahashi, Takashi Nomura, Shimon Sakaguchi, Tomoo Ueno, Yousuke Takahama, Daisuke Uchida, Shijie Sun, Fumiko Kajiura, Yasuhiro Mouri, Hongwei Han, Akemi Matsushima, Gen Yamada and Mitsuru Matsumoto : Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus of Aire-deficient mice, The Journal of Immunology, Vol.174, No.4, 1862-1870, 2005. (Summary) Autoimmune regulator (AIRE) gene mutation is responsible for the development of organ-specific autoimmune disease with monogenic autosomal recessive inheritance. Although Aire has been considered to regulate the elimination of autoreactive T cells through transcriptional control of tissue-specific Ags in thymic epithelial cells, other mechanisms of AIRE-dependent tolerance remain to be investigated. We have established Aire-deficient mice and examined the mechanisms underlying the breakdown of self-tolerance. The production and/or function of immunoregulatory T cells were retained in the Aire-deficient mice. The mice developed Sjogren's syndrome-like pathologic changes in the exocrine organs, and this was associated with autoimmunity against a ubiquitous protein, alpha-fodrin. Remarkably, transcriptional expression of alpha-fodrin was retained in the Aire-deficient thymus. These results suggest that Aire regulates the survival of autoreactive T cells beyond transcriptional control of self-protein expression in the thymus, at least against this ubiquitous protein. Rather, Aire may regulate the processing and/or presentation of self-proteins so that the maturing T cells can recognize the self-Ags in a form capable of efficiently triggering autoreactive T cells. With the use of inbred Aire-deficient mouse strains, we also demonstrate the presence of some additional factor(s) that determine the target-organ specificity of the autoimmune disease caused by Aire deficiency. (Keyword) Animals / Autoantibodies / Autoantigens / Carrier Proteins / Exocrine Glands / Female / Male / Mice / Mice, Inbred BALB C / Mice, Inbred C57BL / Mice, Inbred ICR / Mice, Knockout / Mice, Nude / Microfilament Proteins / Organ Specificity / Polyendocrinopathies, Autoimmune / Self Tolerance / Sjogren's Syndrome / Species Specificity / Stromal Cells / T-Lymphocytes, Regulatory / Thymus Gland / Transcription Factors (Link to Publication Site) ● Publication site (DOI): 10.3410/f.1024264.287833 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15699112 ● Search Scopus @ Elsevier (PMID): 15699112 ● Search Scopus @ Elsevier (DOI): 10.3410/f.1024264.287833 (DOI: 10.3410/f.1024264.287833, PubMed: 15699112)
113.	Masaru Kobayashi, Natsuo Yasui, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : Development of Autoimmune Arthritis With Aging Via Bystander T Cell Activation in the Mouse Model of Sjogren's Syndrome, Arthritis and Rheumatism, Vol.50, No.12, 3974-3984, 2004. (Summary) A wide spectrum of extraglandular manifestations may occur in patients with Sjogren's syndrome (SS), but the mechanisms responsible for in vivo progression are still obscure. We undertook this study to evaluate the age-related changes during the development of extraglandular autoimmune lesions, including arthritis, in the murine model of primary SS, and to evaluate the possible relationship between age-related disturbance of activation-induced cell death and the in vivo kinetics against autoantigens. A total of 126 NFS/sld mice were investigated at ages 2, 4, 6, 10, 12, 18, 20, and 24 months. Cytokine production was tested using culture supernatants from anti-CD3 monoclonal antibody-stimulated T cells. Anti-single-stranded DNA (anti-ssDNA) antibodies, Ig isotypes (IgG1, IgG2a), rheumatoid factor (RF), and anti-type II collagen (anti-CII) antibodies were detected by enzyme-linked immunosorbent assay. Proliferative T cell responses against each of 3 recombinant alpha-fodrin proteins and against CII were analyzed. Autoimmune arthritis developed in SS model mice until age 24 months. Significant elevations in serum levels of RF, anti-ssDNA antibodies, and anti-CII antibodies were found in aging SS model mice. A high titer of serum autoantibodies against alpha-fodrin fragments (containing different epitopes that were originally identified in primary SS model mice) was frequently detected in young and aged SS model mice. Moreover, we found that alpha-fodrin autoantigen induced Th1 immune responses and accelerated disturbance of Fas-mediated T cell apoptosis in aged SS model mice. These results indicate that age-related disturbance of activation-induced cell death via bystander T cell activation may play a crucial role in the development of autoimmune arthritis in a murine model of SS. (Keyword) aging / Animals / apoptosis / Arthritis, Rheumatoid / Autoantigens / Bystander Effect / Carrier Proteins / Cell Proliferation / Culture Media, Conditioned / cytokinesis / Disease Models, Animal / female / Joints / Lymphocyte Activation / Matrix Metalloproteinase 9 / Mice / Mice, Mutant Strains / Microfilament Proteins / Sjögren's syndrome / T lymphocytes (Link to Publication Site) ● Publication site (DOI): 10.1002/art.20679 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15593201 ● Summary page in Scopus @ Elsevier: 2-s2.0-10444278110 (DOI: 10.1002/art.20679, PubMed: 15593201, Elsevier: Scopus)
114.	Yuki Hayashi, Naozumi Ishimaru, Rieko Arakaki, Shin-ichi Tsukumo, Hitomi Fukui, Kenji Kishihara, Hiroshi Shiota, Koji Yasutomo and Yoshio Hayashi : Effective Treatment of a Mouse Model of Sjogren's Syndrome With Eyedrop Administrasiton of Anti-CD4 Monoclonal Antibody, Arthritis and Rheumatism, Vol.50, No.9, 2903-2910, 2004. (Summary) To determine whether eyedrop administration of an anti-CD4 monoclonal antibody (mAb) is effective in the treatment of Sjögren's syndrome (SS) using a mouse model of the disease. The anti-CD4 mAb was administered daily into the eyes of mice with SS from ages 4 to 8 weeks or ages 10 to 12 weeks. During treatment, tear volume was monitored and after final treatment, histologic features of the lacrimal and salivary glands, the phenotypes and function of T cells, and serum titers of anti-alpha-fodrin antibody were examined. Eyedrop administration of anti-CD4 mAb before the onset of SS prevented the autoimmune pathology seen in the lacrimal glands but not that in the salivary glands. Furthermore, eyedrop administration of anti-CD4 mAb after the development of SS inhibited mononuclear cell infiltration and the destruction of parenchyma only in the lacrimal glands. Eyedrop administration of anti-CD4 mAb suppressed the local activation of CD4+ T cells rather than deleting CD4+ T cells, which reduced the expansion of pathologic CD4+ T cells against alpha-fodrin. These results demonstrate the remarkable efficacy of anti-CD4 mAb eyedrops in the treatment of SS eye symptoms, which illustrates a new antibody-based therapeutic strategy for patients with eye problems caused by SS as well as other diseases. (Keyword) Administration, Topical / Animals / Antibodies, Monoclonal / Antigens, CD4 / CD4-Positive T-Lymphocytes / Disease Progression / Dry Eye Syndromes / Female / Lacrimal Apparatus / Lymphocyte Activation / Mice / Models, Animal / Ophthalmic Solutions / salivary glands / Sjögren's syndrome / Treatment Outcome (Link to Publication Site) ● Publication site (DOI): 10.1002/art.20472 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15457459 ● Search Scopus @ Elsevier (PMID): 15457459 ● Search Scopus @ Elsevier (DOI): 10.1002/art.20472 (DOI: 10.1002/art.20472, PubMed: 15457459)
115.	Tomoko Yoneda, Naozumi Ishimaru, Rieko Arakaki, Masaru Kobayashi, Takashi Izawa, Keiji Moriyama and Yoshio Hayashi : Estrogen deficiency accelerates murine autoimmune arthritis associated with receptor activator of nuclear factor-kappaB ligand-mediated osteoclastogenesis, Endocrinology, Vol.145, No.5, 2384-2391, 2004. (Summary) The aims of this study were to evaluate the in vivo effects of estrogen deficiency in MRL/lpr mice as a model for rheumatoid arthritis and to analyze the possible relationship between immune dysregulation and receptor activator of nuclear factor-kappaB ligand (RANKL)-mediated osteoclastogenesis. Experimental studies were performed in ovariectomized (Ovx)-MRL/lpr, Ovx-MRL+/+, sham-operated-MRL/lpr, and sham-operated-MRL+/+ mice. Severe autoimmune arthritis developed in younger Ovx-MRL/lpr mice until 24 wk of age, whereas these lesions were entirely recovered by pharmacological levels of estrogen administration. A significant elevation in serum rheumatoid factor, anti-double-stranded DNA, and anti-type II collagen was found in Ovx-MRL/lpr mice and recovered in mice that underwent estrogen administration. A high proportion of CD4(+) T cells bearing RANKL was found, and an enhanced expression of RANKL mRNA and an impaired osteoprotegerin mRNA was detected in the synovium. An increase in both osteoclast formation and bone resorption pits was found. These results indicate that estrogen deficiency may play a crucial role in acceleration of autoimmune arthritis associated with RANKL-mediated osteoclastogenesis in a murine model for rheumatoid arthritis. (Keyword) Animals / Arthritis / Arthritis, Rheumatoid / Autoimmune Diseases / Bone Resorption / Carrier Proteins / Cytokines / Disease Models, Animal / Estrogens / Female / Gene Expression / Glycoproteins / Joints / Matrix Metalloproteinase 3 / Matrix Metalloproteinase 9 / Membrane Glycoproteins / Mice / Osteoclasts / Osteoprotegerin / Ovariectomy / RANK Ligand / RNA, Messenger / Receptor Activator of Nuclear Factor-kappa B / Receptors, Cytoplasmic and Nuclear / Receptors, Tumor Necrosis Factor / Reverse Transcriptase Polymerase Chain Reaction (Link to Publication Site) ● Publication site (DOI): 10.1210/en.2003-1536 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14726437 ● Search Scopus @ Elsevier (PMID): 14726437 ● Search Scopus @ Elsevier (DOI): 10.1210/en.2003-1536 (DOI: 10.1210/en.2003-1536, PubMed: 14726437)
116.	Hideko Endo, Mitsuyoshi Hirokawa, Naozumi Ishimaru, Yasushi Tanaka, Michiko Yamashita, Mika Sakaki, Yoshio Hayashi and Toshiaki Sano : Unique cell membrane expression if topoisomerase-ll alpha as a useful diagnostic marker of liposarcoma, Pathology International, Vol.54, No.3, 145-150, 2004. (Summary) Topoisomerase-II alpha (Topo-II alpha) is known as a cell cycle-related intranuclear marker. To the best of our knowledge, the expression of Topo-II alpha on extranuclear sites has not been reported. The aim of the present study was to determine the usefulness of Topo-II alpha immunostaining for detecting the lipoblasts that are essential to diagnosing liposarcoma. Surgical specimens, including benign lipomatous tumors (four cases), well-differentiated liposarcomas (three cases), myxoid liposarcomas (six cases), pleomorphic liposarcomas (two cases), dedifferentiated liposarcomas (two cases), myxoid malignant fibrous histiocytomas (six cases), and one case of mesenteric panniculitis, were studied. Samples were immunostained using antibodies for Topo-II alpha, S-100 protein and Ki-67. In addition, we used the western blot method to investigate immunohistochemical-affinity in adipocytes. Mature adipocytes and lipoblasts in all of the benign and malignant lipomatous tumors intensively expressed cell contours positivity for Topo-II alpha. Cytoplasm of the lipoblasts occasionally reacted to the antibody and highlighted intracytoplasmic small unilocular, multivacuolated, or bubble-like patterns. Western blot analysis confirmed a 70 kDa product reactive to Topo-II alpha in the cell membrane fragment of mature adipocytes. S-100 protein expressed adipocytes and lipoblasts, but the detection of lipoblasts was not as easy as in Topo-II alpha immunostaining. Immunoreactivity of Ki-67 was limited to the nuclei, and the nuclear labeling index of Ki-67 correlated with that of Topo-II alpha. The immunoreactivity of Topo-II alpha for lipoblasts was more sensitive and obvious than those of S-100 protein. Immunostaining using the antibody for Topo-II alpha seems to be useful in recognizing lipoblasts that have been overlooked in hematoxylin-eosin-stained preparations, and is a useful marker for diagnosing liposarcoma. (Keyword) adipocytes / lipoblasts / liposarcoma / malignant fibrous histiocytoma / S-100 protein / topoisomerase-ll alpha (Link to Publication Site) ● Publication site (DOI): 10.1111/j.1440-1827.2003.01600.x (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14989736 ● Search Scopus @ Elsevier (PMID): 14989736 ● Search Scopus @ Elsevier (DOI): 10.1111/j.1440-1827.2003.01600.x (DOI: 10.1111/j.1440-1827.2003.01600.x, PubMed: 14989736)
117.	Naozumi Ishimaru, Rieko Arakaki, Nobuhiko Katunuma and Yoshio Hayashi : Critical Role of Cathepsin-Inhibitors for Autoantigen Processing and Autoimmunity, Advances in Enzyme Regulation, Vol.44, No.1, 309-320, 2004. (Keyword) Animals / Autoantigens / Autoimmunity / Cathepsins / Enzyme Inhibitors / Female / Lymph Nodes / Mice / Mice, Inbred C57BL / Mice, Inbred NOD / Mice, Mutant Strains / Spleen / T-Lymphocytes (Link to Publication Site) ● Publication site (DOI): 10.1016/j.advenzreg.2003.11.004 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15581498 ● Search Scopus @ Elsevier (PMID): 15581498 ● Search Scopus @ Elsevier (DOI): 10.1016/j.advenzreg.2003.11.004 (DOI: 10.1016/j.advenzreg.2003.11.004, PubMed: 15581498)
118.	Rieko Arakaki, Naozumi Ishimaru, Ichiro Saito, Masaru Kobayashi, Natsuo Yasui, Takayuki Sumida and Yoshio Hayashi : Development of Autoimmune Exocrinopathy Resembling Sjogren's Syndrome in Adoptively Transferred Mice With Autoreactive CD4+ T Cells, Arthritis and Rheumatism, Vol.48, No.12, 3603-3609, 2003. (Summary) The pathologic mechanisms responsible for organ-specific tissue damage in primary Sjögren's syndrome (SS) remain unclear, but it has been suggested that the pathology is mediated by autoreactive CD4+ T cells infiltrating the salivary and lacrimal glands. This study was undertaken to investigate whether alpha-fodrin autoantigen-specific autoreactive CD4+ T cells are capable of inducing autoimmune lesions. A total of 45 synthetic alpha-fodrin peptides designed to be 20 amino acid residues in length were generated. To establish an autoreactive T cell line, limiting dilution analysis (LDA) was performed on lymph node cells (LNCs) in the presence of alpha-fodrin peptides. The effects of adoptive transfer of autoreactive CD4+ T cells into normal syngeneic recipients were investigated. Autoreactive CD4+ T cell lines that recognize synthetic alpha-fodrin peptide, which produced Th1 cytokines and showed cytotoxic activities, were established in a murine model for SS. T cell receptor V(beta) usage and third complementarity-determining region (CDR3) sequences indicated that in some cases V(beta)6-CDR3 genes matched between the tissue-infiltrating T cells and the autoreactive T cell lines. Adoptive transfer of the autoreactive CD4+ T cells into normal syngeneic recipients induced autoimmune lesions quite similar to those of SS. Our data help to elucidate the pathogenic mechanisms responsible for tissue destruction in autoimmune exocrinopathy and indicate that autoreactive CD4+ T cells play a pivotal role in the development of murine SS. (Keyword) Adoptive Transfer / Amino Acid Sequence / Animals / Base Sequence / CD4-Positive T-Lymphocytes / Carrier Proteins / Complementarity Determining Regions / Disease Models, Animal / Mice / Mice, Mutant Strains / Microfilament Proteins / Molecular Sequence Data / Sjogren's Syndrome / Specific Pathogen-Free Organisms (Link to Publication Site) ● Publication site (DOI): 10.1002/art.11352 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14674013 ● Search Scopus @ Elsevier (PMID): 14674013 ● Search Scopus @ Elsevier (DOI): 10.1002/art.11352 (DOI: 10.1002/art.11352, PubMed: 14674013)
119.	Kouichi Ogawa, Shinji Nagahiro, Rieko Arakaki, Naozumi Ishimaru, Masaru Kobayashi and Yoshio Hayashi : Anti-a-fodrin autoantibodies in Moyamoya disease, Stroke, Vol.34, No.12, 244-246, 2003. (Summary) Moyamoya disease (MMD) is a rare entity that results in progressive occlusion of the arteries of the circle of Willis, but the pathogenesis of MMD is unknown. MMD sera (n=32) were tested for anti-endothelial cell antibodies by enzyme-linked immunoassays and flow cytometric analysis. Apoptosis was induced in human umbilical vein endothelial cells by tumor necrosis factor-alpha. We found that a high proportion of MMD sera had anti-endothelial cell antibodies with apoptotic stimuli. Prominent reactivities of MMD sera (72%) with recombinant human alpha-fodrin were observed. Our study demonstrates that MMD sera contain a high incidence of anti-alpha-fodrin autoantibodies, providing new insight into the mechanisms of occlusion of MMD arteries. (Keyword) α-fodrin / autoantibodies / moyamoya disease (Link to Publication Site) ● Publication site (DOI): 10.1161/01.STR.0000100479.63243.48 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14657555 ● Search Scopus @ Elsevier (PMID): 14657555 ● Search Scopus @ Elsevier (DOI): 10.1161/01.STR.0000100479.63243.48 (DOI: 10.1161/01.STR.0000100479.63243.48, PubMed: 14657555)
120.	Naozumi Ishimaru, Rieko Arakaki, Megumi Watanabe, Kobayashi Masaru, Katsushi Miyazaki and Yoshio Hayashi : Development of autoimmune exocrinopathy resembling Sjogren's syndorome in estorogen deficient mice of healthy background, The American Journal of Pathology, Vol.163, No.4, 1481-1490, 2003. (Summary) Although a number of autoimmune diseases are known to develop in postmenopausal women, the mechanisms by which estrogen deficiency influences autoimmune lesions remain unclear. We speculate that antiestrogenic actions might be a potent factor in the formation of pathogenic autoantigens. Previously, we have identified 120-kd alpha-fodrin as an important autoantigen in Sjögren's syndrome (SS). When healthy C57BL/6 (B6) mice were treated with an ovariectomy (Ovx), we found a significant increase in TUNEL(+)-apoptotic epithelial cells in the salivary gland cells associated with alpha-fodrin cleavage during 2 and 3 weeks after Ovx. By contrast, no apoptotic cells were found in estrogen receptor-alpha knockout mice. In in vitro studies using primary cultured mouse salivary gland cells and human salivary gland cells, we found a cleavage product of 120-kd alpha-fodrin in cells that had undergone tamoxifen (Tam)-induced apoptosis through caspase activation, especially caspase-1. Adoptive transfer of alpha-fodrin-reactive T cells into Ovx-B6 and -SCID mice resulted in the development of autoimmune exocrinopathy quite similar to SS. These results suggest that estrogen deficiency exerts a crucial influence on autoantigen cleavage, and may cause, in part, autoimmune exocrinopathy in postmenopausal women. (Keyword) Adoptive Transfer / Animals / apoptosis / Carrier Proteins / Caspases / Estrogen Receptor alpha / Estrogens / Female / Humans / Mice / Mice, Inbred C57BL / knockout mice / Mice, SCID / Microfilament Proteins / Ovariectomy / Peptide Hydrolases / Receptors, Estrogen / Salivary Gland Diseases / salivary glands / Sjögren's syndrome / T lymphocytes / Tamoxifen / Tumor Cells, Cultured (Link to Publication Site) ● Publication site (DOI): 10.1016/S0002-9440(10)63505-5 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14507655 ● Search Scopus @ Elsevier (PMID): 14507655 ● Search Scopus @ Elsevier (DOI): 10.1016/S0002-9440(10)63505-5 (DOI: 10.1016/S0002-9440(10)63505-5, PubMed: 14507655)
121.	Kaoru Saegusa, Naozumi Ishimaru, Kumiko Yanagi, Rieko Arakaki, Kouichi Ogawa, Ichiro Saito, Nobuhiko Katunuma and Yoshio Hayashi : Cathepsin S-inhibitor prevents autoantigen presentation and autoimmunity, The Journal of Clinical Investigation, Vol.110, No.3, 361-369, 2002. (Summary) The cysteine endoprotease cathepsin S mediates degradation of the MHC class II invariant chain Ii in human and mouse antigen-presenting cells. Studies described here examine the functional significance of cathepsin S inhibition on autoantigen presentation and organ-specific autoimmune diseases in a murine model for Sjögren syndrome. Specific inhibitor of cathepsin S (Clik60) in vitro markedly impaired presentation of an organ-specific autoantigen, 120-kDa alpha-fodrin, by interfering with MHC class II-peptide binding. Autoantigen-specific T cell responses were significantly and dose-dependently inhibited by incubation with Clik60, but not with inhibitor s of cathepsin B or L. Clik60 treatment of mouse salivary gland cells selectively inhibited autopeptide-bound class II molecules. Moreover, the treatment with Clik60 in vivo profoundly blocked lymphocytic infiltration into the salivary and lacrimal glands, abrogated a rise in serum autoantibody production, and led to recovery from autoimmune manifestations. Thus, inhibition of cathepsin S in vivo alters autoantigen presentation and development of organ-specific autoimmunity. These data identify selective inhibition of cysteine protease cathepsin S as a potential therapeutic strategy for autoimmune disease processes. (Keyword) Animals / Antigen Presentation / Antigens, Differentiation, B-Lymphocyte / Autoantigens / Autoimmunity / Carrier Proteins / Cathepsin B / Cathepsin L / Cathepsins / Cell Division / Cysteine Endopeptidases / Disease Models, Animal / Histocompatibility Antigens Class II / Mice / Mice, Inbred C57BL / Microfilament Proteins / Sjogren's Syndrome / T-Lymphocytes (Link to Publication Site) ● Publication site (DOI): 10.1172/JCI14682 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12163455 ● Search Scopus @ Elsevier (PMID): 12163455 ● Search Scopus @ Elsevier (DOI): 10.1172/JCI14682 (DOI: 10.1172/JCI14682, PubMed: 12163455)
122.	Kaoru Saegusa, Naozumi Ishimaru, Kumiko Yanagi, Kenji Mishima, Rieko Arakaki, Takashi Suda, Ichiro Saito and Yoshio Hayashi : Prevention and induction of autoimmune exocrinopathy is dependent on pathogenic autoantigen cleavage in murine Sjogren's syndrome, The Journal of Immunology, Vol.169, No.2, 1050-1057, 2002. (Summary) The in vivo role of autoantigen cleavage during apoptosis in autoimmune diseases remains unclear. Previously, we found a cleavage product of 120-kDa alpha-fodrin as an important autoantigen in the pathogenesis of primary Sjögren's syndrome (SS). In the murine primary SS model, tissue-infiltrating CD4(+) T cells purified from the salivary glands bear a large proportion of Fas ligand, and the salivary gland duct cells constitutively possess Fas. Infiltrating CD4(+) T cells, but not CD8(+) T cells, identified significant (51)Cr release against mouse salivary gland cells. In vitro studies demonstrated that apoptotic mouse salivary gland cells result in a specific alpha-fodrin cleavage into 120 kDa and that preincubation with caspase inhibitor peptides blocked alpha-fodrin cleavage. In vivo treatment with caspase inhibitors N-benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone and N-acetyl-Asp-Glu-Val-Asp-al-CHO into the murine model results in dramatic inhibitory effects on the development of autoimmune lesions and in restoration of sicca syndrome. Furthermore, we found that immunization with recombinant alpha-fodrin protein identical with an autoantigen into normal recipients induced autoimmune lesions similar to SS. These data indicate that prevention and induction of autoimmune exocrinopathy is dependent on autoantigen cleavage via caspase cascade and that caspase inhibitors might provide a new therapeutic option directed at reducing tissue damage in the murine model for SS. (Keyword) NONERYTHROID ALPHA-SPECTRIN / FAS-MEDIATED APOPTOSIS / ICE / CED-3 PROTEASE / POLY(ADP-RIBOSE) POLYMERASE / CPP32-LIKE PROTEASES / MOUSE MODEL / FODRIN / CELLS / MICE / ACTIVATION (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12097413 ● CiNii @ National Institute of Informatics (CRID): 1572543026611280512 ● Search Scopus @ Elsevier (PMID): 12097413 (PubMed: 12097413, CiNii: 1572543026611280512)
123.	Yoshiko Noda, Yukihiro Momota, Kazuhito Satomura, Nobuyuki Kamata, Naozumi Ishimaru and Masaru Nagayama : A case of aspergillosis of the maxillary sinus: discussion of the usefulness of serological examinations, Japanese Journal of Oral & Maxillofacial Surgery, Vol.47, No.12, 811-814, 2001. (Summary) Aspergillosis is caused by infection with <I>Aspergilli</I>. It is often difficult to make an exact diagnosis before identification of <I>Aspergilli</I> by microbial examination because aspergillosis is difficult to differentiate from other diseases. We present a case of aspergillosis of the maxillary sinus that could be diagnosed on serological examination for <I>Aspergilli</I> or fungi specific sugar.<BR>A 51-year-old woman visited to our hospital because of swelling in the gingiva of the maxilla. Radical operation of the maxillary sinus was performed for a clinical diagnosis of aspergillosis of the maxillary sinus. Histopathological examination revealed <I>Aspergilli</I> in the extirpated tissue of the maxillary sinus. Serological examinations showed elevated serum levels of galactomannan and β-D-glucan. Galactomannan is a specific marker for <I>Aspergilli</I>, and β-D-glucan is specific for fungi. Both makers fell to normal levels after operation, Suggesting that serological examinations for galactomannan and β-D-glucan are useful in the diagnosis of aspergillosis of the maxillary sinus. (Keyword) aspergillosis / maxillary sinus / serological examination / galactomannan / β-D-glucan (Link to Publication Site) ● Publication site (DOI): 10.5794/jjoms.47.811 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390001206529635968 ● Search Scopus @ Elsevier (DOI): 10.5794/jjoms.47.811 (DOI: 10.5794/jjoms.47.811, CiNii: 1390001206529635968)
124.	Naozumi Ishimaru, Kumiko Yanagi, Kouichi Ogawa, Takashi Suda, Ichiro Saito and Yoshio Hayashi : Possible Role of Organ-Specific Autoantigen for Fas Ligand-Mediated Activation-Induced Cell Death in Murine Sjögren's Syndrome¹, The Journal of Immunology, Vol.167, No.10, 6031-6037, 2001. (Summary) Activation-induced cell death (AICD) is a well-known mechanism of peripheral T cell tolerance that depends upon an interaction between Fas and Fas ligand (FasL). In this study, we demonstrate that the administration of a soluble form of anti-FasL Ab, FLIM58, results in severe destructive autoimmune exocrinopathy in the murine model of human Sjögren's syndrome (SS), and we found that an organ-specific autoantigen may play an important role on down-modulation of AICD. A high titer of serum autoantibodies against 120-kDa alpha-fodrin autoantigen was detected in the FLIM58-treated mice, and splenic T cell culture supernatants contained high levels of IFN-gamma. In vitro T cell apoptosis assay indicated that FasL-mediated AICD is down-regulated by autoantigen stimulation in spleen cells from the murine SS model, but not from Fas-deficient MRL/lpr mice and FasL-deficient MRL/gld mice. FasL undergo metalloproteinase-mediated proteolytic processing in their extracellular domains, resulting in the release of soluble trimeric ligands (soluble FasL). We showed that the processing of soluble FasL occurs in autoantigen-specific CD4(+) T cells, and that a significant increase in expressions of metalloproteinase-9 mRNA was observed in spleen cells from SS model mice. These findings indicate that the increased generation of soluble FasL inhibits the normal AICD process, leading to the proliferation of effector CD4(+) T cells in the murine SS model. (Keyword) Animals / Antibodies, Monoclonal / Antigens, CD95 / Apoptosis / Autoantibodies / Autoantigens / Carrier Proteins / Cells, Cultured / Cytokines / Fas Ligand Protein / Female / Immunophenotyping / Lymphocyte Activation / Matrix Metalloproteinase 9 / Membrane Glycoproteins / Mice / Microfilament Proteins / Models, Biological / Sjogren's Syndrome / Spleen / T-Lymphocyte Subsets / T-Lymphocytes (Link to Publication Site) ● Publication site (DOI): 10.4049/jimmunol.167.10.6031 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11698484 ● Summary page in Scopus @ Elsevier: 2-s2.0-0035889899 (DOI: 10.4049/jimmunol.167.10.6031, PubMed: 11698484, Elsevier: Scopus)
125.	Kaoru Saegusa, Naozumi Ishimaru, Norio Haneji, Kumiko Yanagi, Tomoko Yoneda, Ichiro Saito and Yoshio Hayashi : Mechanisms of neonatal tolerance induced in an animal model for primary Sjogren's syndrome by intravenous administration of autoantigen, Scandinavian Journal of Immunology, Vol.52, No.3, 264-270, 2000. (Summary) Neonatal exposure to autoantigen is believed to induce effective antigen-specific T-cell tolerance in experimental models of autoimmunity. We have identified 120 kDa alpha-fodrin autoantigen in an animal model for primary Sjögren's syndrome (SS), that has been determined as a candidate autoantigen in both an animal model and the patients with primary SS. We demonstrate here that neonatal injection of autoantigen induce relevant tolerance when treated with intravenous (i.v.) administration within 24 h after birth, but not with i.v. injection after the thymectomy or with intraperitoneal injection. Autoantigen-specific T-cell response was significantly reduced in mice induced neonatal tolerance, and the activation markers of splenic CD4+ T cells were down-regulated in mice treated with neonatal administration. Because we detected that neonatal i.v. injection of autoantigen prevented Th1 response, it is possible that the autoantigen administration within 24 h after birth induce regulatory T cells that had a protective effect against Th1-mediated autoimmune diseases. These results indicate that the prevention of the spontaneous anti-120 kDa alpha-fodrin response in vivo, by tolerization of the autoantigen-reactive T cells, blocked the development of autoimmune lesions in an animal model for primary SS. (Keyword) Animals / Animals, Newborn / Antigens, CD / Autoantigens / Autoimmune Diseases / Carrier Proteins / Cytokines / Disease Models, Animal / Female / Immune Tolerance / Injections, Intravenous / Lymphocyte Activation / Mice / Mice, Mutant Strains / Microfilament Proteins / Recombinant Proteins / Sjogren's Syndrome / Specific Pathogen-Free Organisms / Th1 Cells / Thymectomy (Link to Publication Site) ● Publication site (DOI): 10.1046/j.1365-3083.2000.00777.x (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10972902 ● Summary page in Scopus @ Elsevier: 2-s2.0-0033855846 (DOI: 10.1046/j.1365-3083.2000.00777.x, PubMed: 10972902, Elsevier: Scopus)
126.	Kaoru Saegusa, Naozumi Ishimaru, Kumiko Yanagi, Norio Haneji, Mizuho Nishino, Masayuki Azuma, Ichiro Saito and Yoshio Hayashi : Autoantigen-specific CD4+CD28low T cell subset prevents autoimmune exocrinopathy in murine Sjogren's syndrome, The Journal of Immunology, Vol.165, No.4, 2251-2257, 2000. (Summary) Organ-specific autoimmune exocrinopathy resembling Sjögren's syndrome (SS) that spontaneously develops in NFS/sld mutant mice thymectomized 3 day after birth is dependent on Th1-type CD4+ T cells. We previously reported that a cleavage product of 120-kDa alpha-fodrin may be an important autoantigen in the pathogenesis of SS in both an animal model and the patients. We demonstrate that in an animal model of SS with overt exocrinopathy, a unique CD4+ T cell subset expressing CD28low is dramatically increased in spleen cells before the disease onset, but that the CD4+ T cells of diseased mice were virtually all CD28high. We found that the spleen cells in these mice before the disease onset showed a significant increase in autoantigen-specific T cell proliferation. Analysis of in vitro cytokine production by spleen cells indicated, before the disease onset, severely impaired production of IL-2 and IFN-gamma in the animal model, whereas high levels of IL-4 were observed. Expression of cytokine genes, including IL-4, IL-10, and TGF-beta, was detected in FACS-sorted CD4+CD28low T cells by RT-PCR analysis. Transfer of CD4+CD28low T cells into the animal model actually prevented the development of autoimmune lesions including autoantibody production. These results suggest that a CD4+CD28low T cell subset that is continuously activated by an organ-specific autoantigen may play a regulatory role in the development of organ-specific autoimmune disease in an animal model of SS. (Keyword) Adoptive Transfer / Animals / Autoantigens / CD28 Antigens / CD4-Positive T-Lymphocytes / Carrier Proteins / Cells, Cultured / Epitopes, T-Lymphocyte / Female / Flow Cytometry / Injections, Intraperitoneal / Lymphocyte Activation / Mice / Mice, Inbred BALB C / Mice, Inbred C57BL / Mice, Mutant Strains / Microfilament Proteins / Sjogren's Syndrome / T-Lymphocyte Subsets (Link to Publication Site) ● Publication site (DOI): 10.4049/jimmunol.165.4.2251 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10925313 ● Summary page in Scopus @ Elsevier: 2-s2.0-0034664060 (DOI: 10.4049/jimmunol.165.4.2251, PubMed: 10925313, Elsevier: Scopus)
127.	Keiko Aota, Masayuki Azuma, Tsuyoshi Yamashita, Testuya Tamatani, Katsumi Motegi, Naozumi Ishimaru, Yoshio Hayashi and Mitsunobu Sato : 5-Fluorouracil Induces Apoptosis through the Suppression of NF-κB Activity in Human Salivary Gland Cancer Cells, Biochemical and Biophysical Research Communications, Vol.273, No.3, 1168-1174, 2000. (Summary) Activation of the transcription factor NF-kappaB results in protection against apoptosis, and the chemotherapeutic agent 5-Fluorouracil (5-FU) exerts its cytotoxic effect through the induction of apoptosis. Thus, we examined whether 5-FU could induce apoptosis through the suppression of NF-kappaB activity. We found that upon treatment of a human salivary gland cancer cell line (cl-1) with 5-FU, the NF-kappaB activity was suppressed in a time-dependent manner. This inhibition was mediated by a prevention of the degradation of the inhibitory IkappaB-alpha protein. In addition, the expression of TRAF-2 and cIAP-1, which are transcriptionally regulated by NF-kappaB and function as anti-apoptotic molecules through the interruption of caspase pathway, was also inhibited by 5-FU. Finally, the activity of caspase-8 and caspase-3 showed a significant increase in response to 5-FU. By flow cytometric analysis, 5-FU did not affect the expression level of Fas on the cell surface. Thus, our results suggest that one of the molecular mechanisms involved in 5-FU-induced apoptosis in cl-1 cells may be due to the suppression of NF-kappaB activity, resulting in the activation of the pro-apoptotic pathway. (Keyword) NF-κB / IκB-α / salivary gland cancer cells / 5-FU / apoptosis / TRAF-2 / cIAP-1 / Fas / caspase-8 / caspase-3 (Link to Publication Site) ● Publication site (DOI): 10.1006/bbrc.2000.3072 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10891390 ● Search Scopus @ Elsevier (PMID): 10891390 ● Search Scopus @ Elsevier (DOI): 10.1006/bbrc.2000.3072 (DOI: 10.1006/bbrc.2000.3072, PubMed: 10891390)
128.	Naozumi Ishimaru, Tomoko Yoneda, Kaoru Saegusa, Kumiko Yanagi, Norio Haneji, Keiji Moriyama, Ichiro Saito and Yoshio Hayashi : Severe destructive autoimmune lesions with aging in murine Sjogren's syndrome through Fas-mediated apoptosis, The American Journal of Pathology, Vol.156, No.5, 1557-1564, 2000. (Summary) When we evaluated the age-associated changes in autoimmune exocrinopathy in a NFS/sld murine model for primary Sjögren's syndrome (SS), severe destructive autoimmune lesions developed in the salivary and lacrimal glands in the aged mice, compared with those observed in the younger model. We detected a decreased secretion of saliva and tear flow in the aged group. A significant increase of TUNEL(+)-apoptotic epithelial duct cells in the salivary glands was detected in the aged SS animal model. A higher proportion of mouse salivary gland cells bearing Fas was found in the aged group, whereas no significant changes were seen on tissue-infiltrating CD4(+) T cells bearing FasL in the salivary glands from young and aged mice. We detected an increased cleavage product of organ-specific autoantigen, 120-kd alpha-fodrin, in the aged salivary gland tissues on immunoblotting, and an increase in serum autoantibody production against 120-kd alpha-fodrin by enzyme-linked immunosorbent assay. An increase in the proliferative response of splenic T cells against organ-specific autoantigen was observed, whereas nonspecific concanavalin A responsiveness was decreased in the aged mice. In addition, a decrease in Fas expression was found on splenic CD4(+) T cells in the aged mice, and anti-Fas mAb-stimulated apoptosis was down-regulated on CD4(+) T cells. These results indicate that age-associated dysregulation of CD4(+) T cells may play a crucial role on acceleration of organ-specific autoimmune lesions in a murine model for primary SS through Fas-mediated apoptosis. (Keyword) Aging / Animals / Apoptosis / Autoantibodies / Autoantigens / Autoimmune Diseases / CD4-Positive T-Lymphocytes / Female / In Situ Nick-End Labeling / Male / Mice / Saliva / Sjogren's Syndrome / Tears / fas Receptor (Link to Publication Site) ● Publication site (DOI): 10.1016/S0002-9440(10)65027-4 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10793067 ● Summary page in Scopus @ Elsevier: 2-s2.0-0033843080 (DOI: 10.1016/S0002-9440(10)65027-4, PubMed: 10793067, Elsevier: Scopus)
129.	Kaoru Saegusa, Naozumi Ishimaru, Kumiko Yanagi, Norio Haneji, Mizuho Nishino, Masayuki Azuma and Yoshio Hayashi : Treatment with anti-CD86 costimulatory molecule prevents the autoimmune lesions in murine Sjogren's syndrome (SS) through up-regulated Th2 response, Clinical and Experimental Immunology, Vol.119, No.2, 354-360, 2000. (Keyword) CD86 costimulation / Preventive Effect / α-Fodrin / Autoantigen / Th2 Cytokine / Sjogren's Syndrome
130.	Kaoru Saegusa, Naozumi Ishimaru, Kumiko Yanagai, Norio Haneji, Mizuho Nishino, Masayuki Azuma, Ichiro Saito and Yoshio Hayashi : Treatment with anti-CD 86 costimulatory molecule prevents the autoimmune lesions in murine Sjogren's syndrome(SS) through up-regulated Th2 response, Clinical and Experimental Immunology, Vol.119, 354-360, 2000.
131.	Naozumi Ishimaru, 羽地則雄, 柳久美子 and Yoshio Hayashi : Theraputic effect of fosfomycin in animal model of sjögren's syndrome, Japanese Journal of Chemotherapy, Vol.48, 775-779, 2000. (Link to Publication Site) ● Publication site (DOI): 10.11250/chemotherapy1995.48.775 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-0033758929 (DOI: 10.11250/chemotherapy1995.48.775, Elsevier: Scopus)
132.	Kouji Nitta, Eiji Hayashi, Kenji Fujisawa, Nobuyuki Kamata, Masaru Nagayama, Naozumi Ishimaru and Yoshio Hayashi : Two cases of ameloblastic fibro-odontoma, Japanese Journal of Oral & Maxillofacial Surgery, Vol.46, No.8, 481-483, 2000. (Link to Publication Site) ● Publication site (DOI): 10.5794/jjoms.46.481 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.5794/jjoms.46.481 (DOI: 10.5794/jjoms.46.481)
133.	Naozumi Ishimaru, Kaoru Saegusa, Kumiko Yanagi, Norio Haneji, Ichiro Saito and Yoshio Hayashi : Estrogen Deficiency Accelerates Autoimmune Exocrinopathy in Murine Sjögren's Syndrome through Fas-Mediated Apoptosis, The American Journal of Pathology, Vol.155, No.1, 173-181, 1999.
134.	Naozumi Ishimaru, Kaoru Saegusa, Kumiko Yanagi, Norio Haneji, Ichiro Saito and Yoshio Hayashi : Estrogen dediciency accelerates autoimmune exocrinopathy in murine Sjogren's syndrome through Fas-dediated apoptosis, The American Journal of Pathology, Vol.155, No.1, 173-181, 1999. (Summary) Estrogenic action has been suggested to be responsible for the strong female preponderance of autoimmune diseases, but the role of estrogens in the female has not been well characterized. We evaluated the effects of estrogen deficiency in a murine model for autoimmune exocrinopathy of Sjögren's syndrome (SS). Severe destructive autoimmune lesions developed in the salivary and lacrimal glands in estrogen-deficient mice, and these lesions were recovered by estrogen administration. We detected an intense estrogen receptor in splenic CD8(+) T cells compared with that in CD4(+) T cells, and concanavalin-A-stimulated blastogenesis of splenic CD8(+) T cells with estrogens was much higher than that of CD4(+) T cells. We found a significant increase in serum autoantibody production against the organ-specific autoantigen alpha-fodrin. Moreover, an increased proportion of TUNEL+ apoptotic epithelial duct cells was observed in estrogen-deficient mice. It was demonstrated that Fas-mediated apoptosis in cultured salivary gland cells was clearly inhibited by estrogens in vitro. These results indicate that dysfunction of regulatory T cells by estrogen deficiency may play a crucial role on acceleration of organ-specific autoimmune lesions, and estrogenic action further influences target epithelial cells through Fas-mediated apoptosis in a murine model for SS. (Keyword) Animals / Antigens, CD95 / Apoptosis / Autoimmune Diseases / B-Lymphocytes / Estrogens / Exocrine Glands / Female / Mice / Mice, Mutant Strains / Ovariectomy / Sjogren's Syndrome / T-Lymphocytes / Thymectomy (Link to Publication Site) ● Publication site (DOI): 10.1016/S0002-9440(10)65111-5 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10393849 ● Summary page in Scopus @ Elsevier: 2-s2.0-0032983452 (DOI: 10.1016/S0002-9440(10)65111-5, PubMed: 10393849, Elsevier: Scopus)
135.	Mariko Takahashi, Naozumi Ishimaru, Kumiko Yanagi, Kaoru Saegusa, Norio Haneji, Hiroshi Shiota and Yoshio Hayashi : Requirement for splenic CD4+ T cells in the immune privilege of the anterior chamber of the eye, Clinical and Experimental Immunology, Vol.116, No.2, 231-237, 1999. (Keyword) ACAID / Tolerrance / DTH / CD4+ T cells / Cytokine mRNA
136.	Ichiro Saito, Kumiko Haruta, Misa Shimuta, Hiroko Inoue, Hiroshi Sakurai, Koichi Yamada, Naozumi Ishimaru, Hiroyuki Higashiyama, Takayuki Sumida, Hiroshi Ishida, Takashi Suda, Tetsuo Noda, Yoshio Hayashi and Kazuo Tsubota : Fas ligand-mediated exocrinopathy resembling Sjogren's syndrome in mice transgenic for IL-10, The Journal of Immunology, Vol.162, No.5, 2488-2492, 1999. (Summary) Although IL-10 has been implicated in the pathogenesis of several autoimmune diseases, the mechanisms by which this cytokine mediates inflammatory lesions remain to be elucidated. Exocrine gland destruction is an important early step in the development of Sjögren's syndrome. To better understand the role of IL-10 in Sjögren's syndrome, we made transgenic mice in which the mouse IL-10 gene was regulated by the human salivary amylase promoter. Transgenic expression of IL-10 induced apoptosis of glandular tissue destruction and lymphocyte infiltration consisting primarily of Fas-ligand (FasL)+ CD4+ T cells, as well as in vitro up-regulation of FasL expression on T cells. These data suggest that overexpression of IL-10 in the glands and their subsequent Fas/FasL-mediated bystander tissue destruction is a causal factor in the development of this disease. (Keyword) Animals / Antigens, CD95 / Fas Ligand Protein / Humans / Interleukin-10 / Membrane Glycoproteins / Mice / Mice, Transgenic / Receptors, Antigen, T-Cell, alpha-beta / Reverse Transcriptase Polymerase Chain Reaction / Sjogren's Syndrome (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10072487 ● Summary page in Scopus @ Elsevier: 2-s2.0-0033104634 (PubMed: 10072487, Elsevier: Scopus)
137.	Kazuo Tsubota, Ichiro Saito, Naozumi Ishimaru and Yoshio Hayashi : Use of topical cyclosporin A in a primary Sjogren's syndrome mouse model, Investigative Ophthalmology & Visual Science, Vol.39, No.9, 1551-1559, 1998. (Summary) A new animal model, the NFS/sld mutant mouse, was used for primary Sjögren's syndrome to investigate the efficacy of topical and systemic cyclosporin A (CyA) in preventing inflammation of the exocrine glands. Cyclosporin A was applied topically (0.01% and 0.1%, three times a day) or administered orally (10 mg/kg and 100 mg/kg, once a day) to mice from 6 to 16 weeks of age, after which the mice were killed. Topical CyA reduced lacrimal gland and submandibular gland inflammation without causing pathologic changes in other organs. Flow cytometry showed that CD44 expression of CD4 T cells from the submandibular lymph nodes was downregulated, whereas that of Mel14+ was upregulated. Using a reverse transcription-polymerase chain reaction assay, we determined that topical CyA significantly decreased the expression of mRNA of IL-2 and T-cell receptor-constant beta-chain. Topical CyA may be clinically useful in reducing the lymphocyte infiltration of lacrimal glands associated with Sjögren's syndrome. (Keyword) Administration, Oral / Administration, Topical / Animals / Antigens, CD44 / CD4-Positive T-Lymphocytes / Cyclosporine / DNA Primers / Disease Models, Animal / Female / Flow Cytometry / Immunoenzyme Techniques / Immunosuppressive Agents / Interleukin-2 / Lacrimal Apparatus / Mice / Mice, Inbred BALB C / Mice, Mutant Strains / Ophthalmic Solutions / Polymerase Chain Reaction / RNA, Messenger / Receptors, Antigen, T-Cell, alpha-beta / Sjogren's Syndrome / Submandibular Gland (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9699544 ● Search Scopus @ Elsevier (PMID): 9699544 (PubMed: 9699544)
138.	Kaoru Saegusa, Naozumi Ishimaru, Kumiko Yanagi, Norio Haneji, Mizuho Nishino and Yoshio Hayashi : Mechanisms of transfer into SCID mice reconstituted with tissue-infiltrating cells from murine model for Sjogren's syndrome, Oral Med Pathol, Vol.3, 67-74, 1998. (Keyword) Sjogren's syndrome / cytokine gene / transfer / MRL/ipr mice / SCID mice
139.	Kumiko Yanagi, Naozumi Ishimaru, Norio Haneji, Kaoru Saegusa, Ichiro Saito and Yoshio Hayashi : Anti-120-kDa a-fodrin immune response withTh-1-cytokine profile in the NOD mouse model of Sjogren's syndrome, Eur. J. Immunol., Vol.28, 3336-3345, 1998. (Keyword) Autoantigen / α-fodrin / Cytokine mRNA / NOD mouse / Sjogren's syndrome
140.	Naozumi Ishimaru, Norio Haneji, Hironori Hamano, Kumiko Yanagi, Mariko Takahashi and Yoshio Hayashi : Accelerated onset of age-related autoimmune lesions in MRL/+ mice by ovariectomy, Mechanisms of Ageing and Development, Vol.93, No.1-3, 145-156, 1997. (Keyword) aging patterrn / Autoimmunity / Cytikine gene / Sjogren syndrome / Ovariectomy / MRL/ + mice
141.	Mariko Takahashi, Naozumi Ishimaru, Kumiko Yanagi, Norio Haneji, Ichiro Saito and Yoshio Hayashi : High incidence of autoimmune dacryoadenitis in male non-obese diabetic (NOD) mice depending on sex steroid, Clinical and Experimental Immunology, Vol.109, 555-561, 1997. (Keyword) Sjogren's syndrome / Lacrimal gland / Signal transduction of proinflammatory cytokine receptors / sex steroid / NOD mice
142.	Kumiko Yanagi, Norio Haneji, Naozumi Ishimaru, Ichiro Saito and Yoshio Hayashi : Analysis of T cell receptor Vb usage in the autoimmune sialadenitis of non-obese diabetic (NOD) mice, Clinical and Experimental Immunology, Vol.110, 440-446, 1997. (Keyword) Vβ usage / autoimmune sialadenitis / NOD mouse / Sjogren's syndrome
143.	Yoshio Hayashi, Norio Haneji, Hironori Hamano, Kumiko Yanagi, Mariko Takahashi and Naozumi Ishimaru : Effector Mechanism of Experimental Autoimmune Sialadenitis in the Mouse Model for Primary Sjogren's Syndrome, Cellular Immunology, Vol.171, No.2, 217-225, 1996. (Summary) We have recently established a new animal model for primary Sjögren's syndrome in NFS/sld mutant mice thymectomized 3 days after birth (3dTX) bearing an autosomal recessive gene with sublingual gland differentiation arrest. In this study, we analyze developing mechanisms of experimental autoimmune sialadenitis (EAS) in the mouse model, focusing on local expressions of cytokine and cell adhesion molecule genes by reverse transcriptase-polymeric chain reaction (RT-PCR) and immunohistochemistry, kinetic analysis of splenic lymphocytes expressing activation markers, and I-Aq class-II molecules by flow cytometry (FACS). We found up-regulation of local cytokine genes (IL-1 beta, TNF-alpha, IL-2, IFN-gamma, IL-6, IL-10, IL-12p40) and cell adhesion molecule genes (ICAM-1, LFA-1, CD44, Mel-14) in the salivary glands from mice with EAS by RT-PCR, which were supported by immunohistochemistry. FACS analysis demonstrated that a significant proportion of splenic CD4+ T cells express activation markers (CD44, LFA-1, Mel-14low, CD45RB(low)) at a high level and an increase in expression of B220+ B cells bearing I-Aq class-II molecules. These data suggest that spontaneous EAS in 3dTX NFS/sld mutant mice may be triggered by an in situ activation of autoreactive CD4+ T cells comprising unique cytokine profile (high levels of IL-2, IFN-gamma, IL-10, and IL-12p40 mRNA) in the salivary glands. (Keyword) Animals / autoimmunity / Cell Adhesion Molecules / Cytokines / Disease Models, Animal / Female / Flow Cytometry / gene expression / Immunoenzyme Techniques / Inflammation Mediators / Mice / Mice, Inbred BALB C / Mice, Mutant Strains / Monocytes / salivary glands / Sialadenitis / Sjögren's syndrome / Spleen (Link to Publication Site) ● Publication site (DOI): 10.1006/cimm.1996.0196 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 8806790 ● Search Scopus @ Elsevier (PMID): 8806790 ● Search Scopus @ Elsevier (DOI): 10.1006/cimm.1996.0196 (DOI: 10.1006/cimm.1996.0196, PubMed: 8806790)
144.	Kumiko Yanagi, Norio haneji, Naozumi Ishimaru, Hironori Hamano and Yoshio Hayashi : Immunopathological analysis of mucosal melanocyte distribution in the human lower lip of the elderly, Pathobiology, Vol.64, No.3, 156-160, 1996. (Keyword) Melanocyte / Lower lip / Elderly / Sex difference
145.	Hironori Hamano, Norio Haneji, Kumiko Yanagi, Naozumi Ishimaru and Yoshio Hayashi : Expression of HLA-DR and cytokine genes on interferon-γ-stimulated human salivary gland cell line, Pathobiology, Vol.64, No.5, 255-261, 1996. (Summary) Stimulation of a cultured human salivary gland (HSG) cell line by interferon (IFN)-gamma leads to HLA-DR gene expression concomitant with inflammatory cytokine genes such as IL-1 beta, tumor necrosis factor (TNF)-alpha, and IL-6 in vitro. IFN-gamma-induced HLA-DR mRNA expression was clearly detected at 2 h after the stimulation, and thereafter its level of gene expression increased until day 7 on HSG cells by reverse transcriptase (RT)-PCR. Immunofluorescence analysis revealed that cytoplasmic HLA-DR immunoreactivity was detected for the first time at 2 days after the stimulation, and its immunoreactivity increased gradually until day 7, while no immunoreactivity with HLA-DP and HLA-DQ was observed at any of the days. In addition, the expression of IL-1 beta, TNF-alpha, and IL-6 on the IFN-gamma-stimulated HSG cells was detected by immunohistochemistry and RT-PCR analysis. These results indicate that human salivary gland cells can be induced to express HLA-DR mRNA by IFN-gamma concomitant with inflammatory cytokine gene expressions such as IL-1 beta, TNF-alpha, and IL-6. (Keyword) HLA-DR / Interferon γ / Signal transduction of proinflammatory cytokine receptors / salivary gland (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9068008 ● Search Scopus @ Elsevier (PMID): 9068008 (PubMed: 9068008)
146.	Yoshio Hayashi, Hironori Hamano, Norio Haneji, Naozumi Ishimaru and Kumiko Yanagi : Biased T cell receptor Vβ gene usage during specific stages of the development of autoimmune sialadenitis in the MRL/lpr mouse model of Sjogren's syndrome, Arthritis &Rheumatism, Vol.38, No.8, 1077-1084, 1995.

Academic Paper (Unrefereed Paper):

1.	Daishiroh Kobayashi, Masaya Denda, JUNYA Hayashi, Kohta Hidaka, Yutaka Kohmura, Takaaki Tsunematsu, Kohei Nishino, Harunori Yoshikawa, OHKAWACHI Kento, Kiyomi Nigorikawa, Tetsuro Yoshimaru, Naozumi Ishimaru, Nomura Wataru, Toyomasa Katagiri, Hidetaka Kosako and Akira Otaka : Sulfoxide-mediated Cys-Trp-selective bioconjugation that enables protein labeling and peptide heterodimerization, ChemRxiv, 2024. (Link to Publication Site) ● Publication site (DOI): 10.26434/chemrxiv-2024-tkv7w-v2 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.26434/chemrxiv-2024-tkv7w-v2 (DOI: 10.26434/chemrxiv-2024-tkv7w-v2)
2.	Naozumi Ishimaru, 岸本英博, Yoshio Hayashi and Sprent Jonathan : NF-kB2によるT細胞の新たな調節機構, 実験医学月刊, Vol.24, No.16, 2513-2516, 2006.
3.	Yoshio Hayashi, Naozumi Ishimaru and Rieko Arakaki : RbAp48遺伝子導入マウスにおけるシェーグレン症候群様病態の出現, Clinical Immunology, Vol.45, No.5, 533-537, 2006.

Academic Letter:

1.	Hidesuke Tada, Wenhua Shao, Naozumi Ishimaru and Yasusei Kudo : The life in Japan and status of private dental office at the times of COVID-19., Oral Diseases, Vol.27 Suppl 3, 727-729, 2020. (Keyword) COVID-19 / Dental Offices / Humans / Japan / SARS-CoV-2 (Tokushima University Institutional Repository) ● Metadata: 114968 (Link to Publication Site) ● Publication site (DOI): 10.1111/odi.13449 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32475028 ● Summary page in Scopus @ Elsevier: 2-s2.0-85087066066 (Tokushima University Institutional Repository: 114968, DOI: 10.1111/odi.13449, PubMed: 32475028, Elsevier: Scopus)
2.	Naozumi Ishimaru : [Oral immune system and oral immune disorder.], Clinical Calcium, Vol.27, No.10, 1363-1368, 2017. (Summary) Oral immune system is maintained by various lymphoid tissues in head and neck region and efficient function of oral mucosa and saliva. A variety of oral immune disorders such as infection, allergic disease and autoimmune disease are induced by dysfunction of oral immune system. Sjogren's syndrome is an autoimmune disease that affects exocrine glands, including salivary glands, causing dry mouth symptoms. Because the pathogenesis of Sjogren's syndrome is complex, the study with multiple approaches using many models has been developed to understand the precise mechanism of the disease onset. (Keyword) Autoimmune Diseases / Humans / Immune System / Mouth Diseases / Mouth Mucosa (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28947686 ● Search Scopus @ Elsevier (PMID): 28947686 (PubMed: 28947686)

Review, Commentary:

1.	Hiromichi Yumoto, Yoshiko Yamamura, Naozumi Ishimaru and Youji Miyamoto : Dd診断力てすと歯肉と頬粘膜の白色病変, デンタルダイアモンド, Vol.48, No.5, 25-26, Apr. 2023.
2.	Katsushi Miyazaki, Naozumi Ishimaru, Yoshio Hayashi and Noriaki Takeda : Role of α-Fodrin Autoantigen in Sjogren's Syndrome, Practica Oto-Rhino-Laryngologica. Suppl., No.158, 119-121, Feb. 2022. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390855035383478144 (CiNii: 1390855035383478144)
3.	Kunihiro Otsuka and Naozumi Ishimaru : A role of follicular helper T cell in the pathogenesis of Sjogren's syndrome, Clinical Immunology & Allergology, Vol.73, No.3, 241-248, Mar. 2020. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1521699230266946688 (CiNii: 1521699230266946688)
4.	M Samadarani B S Siriwardena, Takaaki Tsunematsu, Guangying Qi, Naozumi Ishimaru and Yasusei Kudo : Invasion-Related Factors as Potential Diagnostic and Therapeutic Targets in Oral Squamous Cell Carcinoma-A Review., International Journal of Molecular Sciences, Vol.19, No.5, May 2018. (Summary) It is well recognized that the presence of cervical lymph node metastasis is the most important prognostic factor in oral squamous cell carcinoma (OSCC). In solid epithelial cancer, the first step during the process of metastasis is the invasion of cancer cells into the underlying stroma, breaching the basement membrane (BM)-the natural barrier between epithelium and the underlying extracellular matrix (ECM). The ability to invade and metastasize is a key hallmark of cancer progression, and the most complicated and least understood. These topics continue to be very active fields of cancer research. A number of processes, factors, and signaling pathways are involved in regulating invasion and metastasis. However, appropriate clinical trials for anti-cancer drugs targeting the invasion of OSCC are incomplete. In this review, we summarize the recent progress on invasion-related factors and emerging molecular determinants which can be used as potential for diagnostic and therapeutic targets in OSCC. (Tokushima University Institutional Repository) ● Metadata: 112412 (Link to Publication Site) ● Publication site (DOI): 10.3390/ijms19051462 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29758011 ● Summary page in Scopus @ Elsevier: 2-s2.0-85047065487 (Tokushima University Institutional Repository: 112412, DOI: 10.3390/ijms19051462, PubMed: 29758011, Elsevier: Scopus)
5.	Guangying Qi, Jing Liu, Sisi Mi, Takaaki Tsunematsu, Shengjian Jin, Wenhua Shao, Tian Liu, Naozumi Ishimaru, Bo Tang and Yasusei Kudo : Aurora Kinase Inhibitors In Head And Neck Cancer., Current Topics in Medicinal Chemistry, Vol.18, No.3, 199-213, Jan. 2018. (Summary) Aurora kinases are a group of serine/threonine kinases responsible for the regulation of mitosis. In recent years, with the increase in Aurora kinase-related research, the important role of Aurora kinases in tumorigenesis has been gradually recognized. Aurora kinases have been regarded as a new target for cancer therapy, resulting in the development of Aurora kinase inhibitors. The study and application of these small-molecule inhibitors, especially in combination with chemotherapy drugs, represents a new direction in cancer treatment. This paper reviews studies on Aurora kinases from recent years, including studies of their biological function, their relationship with tumor progression, and their inhibitors. (Tokushima University Institutional Repository) ● Metadata: 113572 (Link to Publication Site) ● Publication site (DOI): 10.2174/1568026618666180112163741 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29332580 ● Summary page in Scopus @ Elsevier: 2-s2.0-85047777413 (Tokushima University Institutional Repository: 113572, DOI: 10.2174/1568026618666180112163741, PubMed: 29332580, Elsevier: Scopus)
6.	Masako Saito, Kunihiro Otsuka, Aya Ushio, Akiko Yamada, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : Unique Phenotypes and Functions of Follicular Helper T Cell and Regulatory T Cell in Sjögren's Syndrome., Current Rheumatology Reviews, Vol.14, No.3, 239-245, Jan. 2017. (Summary) Sjögren's syndrome (SS) is a T cell-mediated autoimmune disease of the systemic exocrine glands, such as salivary and lacrimal glands. A variety of T-cell subpopulations maintain immune tolerance in the thymus and periphery through complex immune responses including cellular and humoral immunity. The T-cell subpopulations exhibiting abnormal or unique phenotypes and impaired functionality have been reported to play important roles in the cellular mechanisms of autoimmunity in SS patients and animal models of SS. In this review, we focused on follicular helper T cells related to antibody production and regulatory T cells to control immune tolerance in the pathogenesis of SS. The unique roles of these T-cell subpopulations in the process of the onset or development of SS have been demonstrated in this review of recent publications. The clinical application of these T-cell subpopulations will be helpful for the development of new techniques for diagnosis or treatment of SS in the future. (Keyword) Animals / Autoimmunity / Disease Models, Animal / Humans / Immune Tolerance / Lymph Nodes / Phenotype / Sjogren's Syndrome / T-Lymphocytes, Helper-Inducer / T-Lymphocytes, Regulatory (Link to Publication Site) ● Publication site (DOI): 10.2174/1573397113666170125122858 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28124612 ● Search Scopus @ Elsevier (PMID): 28124612 ● Search Scopus @ Elsevier (DOI): 10.2174/1573397113666170125122858 (DOI: 10.2174/1573397113666170125122858, PubMed: 28124612)
7.	Yasusei Kudo, Tada Hidesuke, Natsumi Fujiwara, Tada Yoshiko, Takaaki Tsunematsu, Yoichiro Miyake and Naozumi Ishimaru : Oral environment and cancer, Genes and Environment, Vol.38, No.13, Aug. 2016. (Summary) Cancer is now the leading cause of death in Japan. A rapid increase in cancer mortality is expected as Japan is facing a super-aged society. Many causes of cancer are known to be closely linked to life style factors, such as smoking, drinking, and diet. The oral environment is known to be involved in the pathogenesis and development of various diseases such as bronchitis, pneumonia, diabetes, heart disease, and dementia. Because the oral cavity acts as the bodily entrance for air and food, it is constantly exposed to foreign substances, including bacteria and viruses. A large number of bacteria are endemic to the oral cavity, and indigenous oral flora act to prevent the settlement of foreign bacteria. The oral environment is influenced by local factors, including dental plaque, tartar, teeth alignment, occlusion, an incompatible prosthesis, and bad lifestyle habits, and systemic factors, including smoking, consumption of alcohol, irregular lifestyle and eating habits, obesity, stress, hormones, and heredity. It has recently been revealed that the oral environment is associated with cancer. In particular, commensal bacteria in the oral cavity are involved in the development of cancer. Moreover, Candida, human papilloma virus and Epstein-Barr virus as well as commensal bacteria have been reported to be associated with the pathogenesis of cancer. In this review, we introduce recent findings of the correlation between the oral environment and cancer. (Keyword) cancer / Oral environment / bacteria / Candida / Human papilloma virus / Epstein-Barr virus (Tokushima University Institutional Repository) ● Metadata: 114519 (Link to Publication Site) ● Publication site (DOI): 10.1186/s41021-016-0042-z (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27482300 ● Search Scopus @ Elsevier (PMID): 27482300 ● Search Scopus @ Elsevier (DOI): 10.1186/s41021-016-0042-z (Tokushima University Institutional Repository: 114519, DOI: 10.1186/s41021-016-0042-z, PubMed: 27482300)
8.	Akiko Yamada, Rieko Arakaki, Masako Saito, Takaaki Tsunematsu, Yasusei Kudo and Naozumi Ishimaru : Role of regulatory T cell in the pathogenesis of inflammatory bowel disease., World Journal of Gastroenterology : WJG, Vol.22, No.7, 2195-2205, Feb. 2016. (Summary) Regulatory T (Treg) cells play key roles in various immune responses. For example, Treg cells contribute to the complex pathogenesis of inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis during onset or development of that disease. Many animal models of IBD have been used to investigate factors such as pathogenic cytokines, pathogenic bacteria, and T-cell functions, including those of Treg cells. In addition, analyses of patients with IBD facilitate our understanding of the precise mechanism of IBD. This review article focuses on the role of Treg cells and outlines the pathogenesis and therapeutic strategies of IBD based on previous reports. (Tokushima University Institutional Repository) ● Metadata: 110976 (Link to Publication Site) ● Publication site (DOI): 10.3748/wjg.v22.i7.2195 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26900284 ● Summary page in Scopus @ Elsevier: 2-s2.0-84959872333 (Tokushima University Institutional Repository: 110976, DOI: 10.3748/wjg.v22.i7.2195, PubMed: 26900284, Elsevier: Scopus)
9.	Rieko Arakaki, Akiko Yamada, Yasusei Kudo, Yoshio Hayashi and Naozumi Ishimaru : Mechanism of Activation-Induced Cell Death of T Cells and Regulation of FasL Expression., Critical Reviews in Immunology, Vol.34, No.4, 301-314, May 2014. (Summary) Activation-induced cell death (AICD) of T cells is a process for regulating the peripheral immune system. The fate of a T cell is controlled by numerous signals derived from various stimuli, such as antigens, cytokines, and chemokines. In healthy humans, overactivated or autoreactive T cells are harmful and are eliminated to maintain the immune system. AICD in T cells by Fas/FasL-mediated apoptosis is triggered by the switch from life to death through several signaling molecules. The control or distribution of Fas or FasL expression largely affects AICD of T cells. Although autoimmune diseases are considered to be induced by multiple factors, an impaired immune system with AICD by Fas/FasL-mediated apoptosis leads to the onset or development of autoimmunity. Based on published reports, this review describes the regulatory mechanisms involved in AICD of T cells by Fas/ FasL-mediated apoptosis and the associations between AICD and autoimmunity in humans and animal models. (Keyword) Animals / Antigens, CD95 / Apoptosis / Autoimmune Diseases / Cytokines / Disease Models, Animal / Fas Ligand Protein / Gene Expression Regulation / Humans / Immune System Diseases / Lymphocyte Activation / T-Lymphocyte Subsets (Link to Publication Site) ● Publication site (DOI): 10.1615/CritRevImmunol.2014009988 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24941158 ● Summary page in Scopus @ Elsevier: 2-s2.0-84902530588 (DOI: 10.1615/CritRevImmunol.2014009988, PubMed: 24941158, Elsevier: Scopus)
10.	Shinji Iizuka, Naozumi Ishimaru and Yasusei Kudo : Matrix metalloproteinases: the gene expression signatures of head and neck cancer progression., Cancers, Vol.6, No.1, 396-415, Feb. 2014. (Summary) Extracellular matrix degradation by matrix metalloproteinases (MMPs) plays a pivotal role in cancer progression by promoting motility, invasion and angiogenesis. Studies have shown that MMP expression is increased in head and neck squamous cell carcinomas (HNSCCs), one of the most common cancers in the world, and contributes to poor outcome. In this review, we examine the expression pattern of MMPs in HNSCC by microarray datasets and summarize the current knowledge of MMPs, specifically MMP-1, -3, -7 -10, -12, -13, 14 and -19, that are highly expressed in HNSCCs and involved cancer invasion and angiogenesis. (Tokushima University Institutional Repository) ● Metadata: 113577 (Link to Publication Site) ● Publication site (DOI): 10.3390/cancers6010396 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24531055 ● Summary page in Scopus @ Elsevier: 2-s2.0-84894098127 (Tokushima University Institutional Repository: 113577, DOI: 10.3390/cancers6010396, PubMed: 24531055, Elsevier: Scopus)
11.	Akiko Yamada, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : Targeting IL-1 in Sjögren's syndrome., Expert Opinion on Therapeutic Targets, Vol.17, No.4, 393-401, Jan. 2013. (Summary) Introduction: IL-1 plays key roles in the biological functions of various cells. In particular, many roles of IL-1 in the immune system have been discovered by numerous studies. This review focuses on the association of IL-1 with the pathogenesis of autoimmunity. Areas covered: An overview of the biological functions of the IL-1 family and the IL-1 receptors (IL-1Rs), including the maintenance of systemic or local homeostasis, and the signaling pathway through IL-1/IL-1R in various immune systems are described. Several functions of IL-1 in the pathogenesis of Sjögren's syndrome (SS) have been demonstrated with a focus on the immune responses and target tissues in SS. In addition to the role of IL-1 in the immune responses in SS, the function of IL-1 in ocular mucosa lesions in SS has been described. Lastly, there is an overview of possible therapeutic strategies for IL-1 inhibition in SS. Expert opinion: IL-1 plays critical roles in the onset and development of SS by controlling systemic or local immune responses and maintaining the survival and mucosal defense of target epithelial cells. The inhibition of the pathogenic functions of IL-1 may be beneficial for treating SS. (Link to Publication Site) ● Publication site (DOI): 10.1517/14728222.2013.754427 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23320392 ● Search Scopus @ Elsevier (PMID): 23320392 ● Search Scopus @ Elsevier (DOI): 10.1517/14728222.2013.754427 (DOI: 10.1517/14728222.2013.754427, PubMed: 23320392)
12.	Yoshio Hayashi, Rieko Arakaki and Naozumi Ishimaru : Sjogren's syndrome, The Journal of the Japanese Society of Internal Medicine, Vol.100, No.5, 1262-1268, Jun. 2011. (Summary) Sjögren症候群はドライアイやドライマウスを臨床症状とする原因不明の自己免疫疾患である．病因的アプローチを加えるため疾患モデルを開発し，ヒトとも共通する自己抗原120kDα-フォドリンを同定した．局所に浸潤するCD4陽性T細胞の多くがFasLを発現し，標的細胞のFas抗原との間でアポトーシスが成立している．また，唾液腺にエストロゲン欠乏依存性にアポトーシスを誘導するRbAp48遺伝子を同定した． (Keyword) Sjogren 症候群 / 自己抗原 / 疾患モデル (Link to Publication Site) ● Publication site (DOI): 10.2169/naika.100.1262 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390282681421664640 ● Summary page in Scopus @ Elsevier: 2-s2.0-79961164769 (DOI: 10.2169/naika.100.1262, CiNii: 1390282681421664640, Elsevier: Scopus)
13.	Naozumi Ishimaru, Takashi Izawa and Yoshio Hayashi : Regulation of immune response by RANKL and Fas, Clinical Immunology & Allergology, Vol.55, No.2., 142-147, Apr. 2011. (Keyword) RANKL / Fas / dendritic cell / autoimmunity (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1523669555532217472 (CiNii: 1523669555532217472)
14.	Rieko Arakaki, Naozumi Ishimaru and Yoshio Hayashi : Immunotherapeutic targets in estrogen deficiency-dependent Sjögren's syndrome-related manifestations, Immunotherapy, Vol.2, No.3, 339-346, May 2010. (Summary) Although a number of autoimmune diseases are known to develop in postmenopausal women, the mechanisms by which estrogen deficiency influences autoimmunity remain unclear. Previously, we found that tissue-specific apoptosis in the exocrine glands in estrogen-deficient mice may contribute to the development of autoimmune exocrinopathy. We found that RbAp48 overexpression induces p53-mediated apoptosis in the exocrine glands depending on estrogen deficiency. RbAp48-inducible transfectants result in rapid apoptosis with p53 phosphorylation (Ser9), and alpha-fodrin cleavage. Indeed, transgenic expression of the RbAp48 gene induced apoptosis in the exocrine glands, resulting in the development of autoimmune exocrinopathy resembling Sjögren's syndrome (SS). CD4(+) T-cell-mediated autoimmune lesions were aggravated with age, in association with production of autoantibodies against SS-A, SS-B and alpha-fodrin. These findings demonstrated that estrogen deficiency initiates tissue-specific apoptosis in the exocrine gland cells through RbAp48 overexpression and exerts a possible gender-based risk of autoimmune exocrinopathy in postmenopausal women. Thus, these data indicate RbAp48 to be a novel immunotherapeutic target for preventing epithelial cell apoptosis and the development of gender-based autoimmune exocrinopathy. (Keyword) Animals / Apoptosis / Estrogens / Female / Humans / Immunotherapy / Mice / Mice, Transgenic / Retinoblastoma-Binding Protein 4 / Salivary Glands / Sjogren's Syndrome (Link to Publication Site) ● Publication site (DOI): 10.2217/imt.10.18 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20635899 ● Search Scopus @ Elsevier (PMID): 20635899 ● Search Scopus @ Elsevier (DOI): 10.2217/imt.10.18 (DOI: 10.2217/imt.10.18, PubMed: 20635899)
15.	Takashi Izawa, Naozumi Ishimaru, Eiji Tanaka and Yoshio Hayashi : Crosstalk between RANKL and Fas signaling in dendritic cells controls immune tolerance, Clinical Immunology & Allergology, Vol.52, No.5, 471-477, Nov. 2009. (Keyword) RANK/RANKL signal / Fas/FasL signal / dendritic cell / apoptosis / rheumatoid arthritis / rank/rankl signal / fas/fasl signal (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1522543655149137152 (CiNii: 1522543655149137152)
16.	Naozumi Ishimaru, 岸本英博, Yoshio Hayashi and Sprent Jonathan : NF-kB2によるT細胞の新たな調節機構, Experimental Medicine, Vol.24, No.16, 2513-2516, Jan. 2007.
17.	Naozumi Ishimaru and Yoshio Hayashi : Crucial Roles of NF-κB for T Cell Activation, Journal of Oral Biosciences, Vol.48, No.1, 12-17, Feb. 2006. (Link to Publication Site) ● Publication site (DOI): 10.1016/S1349-0079(06)80014-9 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-85009571086 (DOI: 10.1016/S1349-0079(06)80014-9, Elsevier: Scopus)
18.	Yoshio Hayashi, Rieko Arakaki and Naozumi Ishimaru : エストロゲンと自己免疫疾患, Annual Review糖尿病・代謝・内分泌2006, 241-246, Jan. 2006.
19.	Yoshio Hayashi, Naozumi Ishimaru and 表原文江 : 唾液腺の自己免疫病変, 病理と臨床, No.25, 116-121, 2005.
20.	Yoshio Hayashi, Naozumi Ishimaru and Fumie Omotehara : 唾液腺の自己免疫病変, 病理と臨床, Vol.23, 116-121, 2005.
21.	Yoshio Hayashi, Rieko Arakaki and Naozumi Ishimaru : Crucial Role of Tissue-Specific Apoptosis on the Development of Primary Sjogren's Syndrome, Oral Science International, Vol.1, No.2, 55-64, Nov. 2004. (Keyword) Sjögren's syndrome / apoptosis / Autoantigen / Activation-Induced Cell Death(AICD) / Estrogen Deficiency (Link to Publication Site) ● Publication site (DOI): 10.1016/S1348-8643(04)80007-7 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1570572700257558784 ● Search Scopus @ Elsevier (DOI): 10.1016/S1348-8643(04)80007-7 (DOI: 10.1016/S1348-8643(04)80007-7, CiNii: 1570572700257558784)
22.	Yoshio Hayashi, Rieko Arakaki and Naozumi Ishimaru : Apoptosis and Estrogen Deficiency in Primary Sjögren Syndrome, Current Opinion in Rheumatology, Vol.16, No.5, 522-526, Sep. 2004. (Summary) Primary Sjögren syndrome is an autoimmune disorder characterized by lymphocytic infiltrates and destruction of the salivary and lacrimal glands, and systemic production of autoantibodies to the ribonucleoprotein particles SS-A/Ro and SS-B/La. The purpose of this review is to discuss recent advances in the pathogenesis of primary Sjögren syndrome. Although several candidate autoantigens including alpha-fodrin have been reported in Sjögren syndrome, the pathogenic roles of the autoantigens in initiation and progression of SS are still unclear. It is possible that individual T cells activated by an appropriate self antigen can proliferate and form a restricted clone. Recent evidence suggests that the apoptotic pathway plays a central role in tolerizing T cells to tissue-specific self antigen, and may drive the autoimmune phenomenon. Cleavage of certain autoantigens during apoptosis may reveal immunocryptic epitopes that could potentially induce autoimmune response. The studies reviewed imply that Fas-mediated cytotoxicity and caspase-mediated alpha-fodrin proteolysis are involved in the progression of tissue destruction in Sjögren syndrome. Fas ligand (FasL), and its receptor Fas are essential in the homeostasis of the peripheral immune system. It can be considered that a defect in activation-induced cell death of effector T cells may result in the development of autoimmune exocrinopathy in Sjögren syndrome. Although the mechanisms by which estrogen deficiency influences autoimmune lesions remain unclear, it is possible that antiestrogenic actions might be a potent factor in the formation of pathogenic autoantigens. (Keyword) Animals / Apoptosis / Carrier Proteins / Estrogens / Female / Humans / Male / Microfilament Proteins / Sjogren's Syndrome / T-Lymphocytes (Link to Publication Site) ● Publication site (DOI): 10.1097/01.bor.0000135450.78047.78 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15314488 ● Search Scopus @ Elsevier (PMID): 15314488 ● Search Scopus @ Elsevier (DOI): 10.1097/01.bor.0000135450.78047.78 (DOI: 10.1097/01.bor.0000135450.78047.78, PubMed: 15314488)
23.	Yoshio Hayashi, Hitomi Fukui and Naozumi Ishimaru : Aging and Autoimmune Diseases, 日本アフェレシス学会雑誌, Vol.23, No.2, 176-181, May 2004. (Keyword) aging / immune / function / thymus / T-cell
24.	Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : 自己免疫疾患の発症とアポトーシス, The Cell, Vol.35, 20-23, Aug. 2003. (Keyword) apoptosis / salivary gland / autoantigen / T cell / AICD (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520291853565301888 (CiNii: 1520291853565301888)
25.	Yoshio Hayashi, Rieko Arakaki and Naozumi Ishimaru : The role of caspase cascade on the development of primary Sjogren's syndrome, The Journal of Medical Investigation : JMI, Vol.50, No.1,2, 32-38, Feb. 2003. (Summary) Primary Sjögren syndrome (SS) is an autoimmune disease characterized by diffuse lymphoid cell infiltrates in the salivary and lacrimal glands, resulting in symptoms of dry eye and dry mouth due to insufficient secretion. Previously, we have identified the 120 kDa alpha-fodrin as an important autoantigen on the development of SS in both animal model and SS patients, but the mechanism of a -fodrin cleavage leading to tissue destruction in SS remains unclear. In murine primary SS model, tissue-infiltrating CD4+ T cells purified from the salivary glands bear a large proportion of Fas ligand (FasL), and the salivary gland duct cells constitutively possess Fas. Infiltrating CD4+ T cells identified significant 51Cr release against mouse salivary gland (MSG) cells. In vitro studies demonstrated that apoptotic MSG cells result in a specific alpha-fodrin cleavage into 120 kDa, and preincubation with caspase-inhibitor peptides blocked alpha-fodrin cleavage. The treatment with caspase-inhibitors in vivo prevented the development of autoimmune lesions in the salivary and lacrimal glands. Thus, an increased activity in caspase cascade may be involved in the progression of alpha-fodrin proteolysis and tissue destruction on the development of SS. (Keyword) Animals / Antigens, CD95 / Apoptosis / Autoantigens / Autoimmune Diseases / CD4-Positive T-Lymphocytes / Carrier Proteins / Caspase 3 / Caspases / Cysteine Proteinase Inhibitors / Disease Models, Animal / Fas Ligand Protein / Humans / Immunization / Membrane Glycoproteins / Mice / Mice, Inbred C57BL / Mice, Inbred MRL lpr / Mice, Inbred NOD / Mice, Mutant Strains / Microfilament Proteins / Recombinant Proteins / Salivary Ducts / Salivary Glands / Sjogren's Syndrome (Tokushima University Institutional Repository) ● Metadata: 110675 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12630566 ● Search Scopus @ Elsevier (PMID): 12630566 (Tokushima University Institutional Repository: 110675, PubMed: 12630566)
26.	Yoshio Hayashi, Rieko Arakaki and Naozumi Ishimaru : シェーグレン症候群発症の分子機構, Clinical Immunology, Vol.40, 196-204, 2003.
27.	渡辺恵, 市川哲雄, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : 接触性過敏症における樹状細胞の役割, アレルギー科, Vol.15, 481-487, 2003.
28.	Yoshio Hayashi and Naozumi Ishimaru : 自己免疫疾患における分子模倣仮説, Journal of Clinical and Experimental Medicine, Vol.206, 855-858, 2003.
29.	Yoshio Hayashi, Rieko Arakaki and Naozumi Ishimaru : シェ-グレン症候群発症の分子機構, Clinical Immunology, Vol.40, 196-204, 2003.
30.	Yoshio Hayashi, 柳久美子 and Naozumi Ishimaru : 免疫異常からみたリウマチ性疾患の臓器病変:口腔内病変, リウマチ科, Vol.21, 630-638, 1999.

Proceeding of International Conference:

1.	Naozumi Ishimaru : Chronic Immunotoxicity of Multi-Walled Carbon Nanotubes on Macrophages via MMP-12, Inhaled Particles/NanOEHconference2023, Manchester, May 2023.
2.	Takaaki Tsunematsu, Naozumi Ishimaru and Yasusei Kudo : APC/CCdh1-mediated degradation of Borealin triggers differentiation of pluripotent stem cells., FASEB meeting Ubiquitin and Cellular Regulation, Snowmass Village, CO, USA, May 2018.
3.	Kunihiro Ohtsuka, Akiko Yamada, Masako Saito, Aya Ushio, Takaaki Tsunematsu, Rieko Arakaki, Yasusei Kudo, Hidehiro Kishimmoto and Naozumi Ishimaru : Analysis of follicular helper T cells in a mouse model for Sjogren's Syndorome., 11th International Congress of Autoimmunity, Lisbon, May 2018.
4.	Aya Ushio, Rieko Arakaki, Kunihiro Ohtsuka, Yasusei Kudo and Naozumi Ishimaru : CCL22Producing Resident Macrophages Enhances InflaMMation in Salivary Glands of Sjogren's Syndorome., 11th International Congress of Autoimmunity, Lisbon, May 2018.
5.	Rieko Arakaki, Aya Ushio, Kunihiro Ohtsuka, Yasusei Kudo and Naozumi Ishimaru : NF-kB2 Controls the Migratory of Memory T cells to the Target Tissues in a Mouse Model of Sjogren's Syndorome by Regulating Expression of CXCR4., 11th International Congress of Autoimmunity, Lisbon, May 2018.
6.	Junhel Dalanon, S Afroz, Takuma Iwasa, Rieko Arakaki, Masamitsu Oshima, Naozumi Ishimaru and Yoshizo Matsuka : Cytokine involvement in orofacial neuralgia: fundamental research, Asia Pacific Dental Congress, Manila, May 2018.
7.	Takashi Izawa, Rieko Arakaki and Naozumi Ishimaru : Signal crosstalk between cytokine RANKL and AhR signaling in osteoclasts controls bone homeostasis, The Journal of Immunology, Vol.Supplement, No.43.15, 25, Austin, May 2018. (Keyword) osteoclast / RANKL
8.	Naozumi Ishimaru, Mie Kurosawa, Rieko Arakaki, Aya Ushio, otsuka kunihiro and Yasusei Kudo : Contributions of CXCL12 and its receptor to the T cell autoimmune response in a Sjögren's syndrome murine model., 14th International Symposium on Sjögren's Syndrome, Washington, D.C., Apr. 2018.
9.	Takashi Izawa, Rieko Arakaki, Eiji Tanaka and Naozumi Ishimaru : Crosstalk between cytokine RANKL and AhR signaling in osteoclasts controls bone homeostasis, Gordon Research Conference; "Bones and Teeth" From Skeletal and Dental Stem Cells to Rare Bone Disease and Integrative Physiology, Houston, Jan. 2018. (Keyword) osteoclast / RANKL
10.	Iwasa Takuma, Rieko Arakaki, Oshima Masamitsu, S Afroz, Miho Inoue, Goto Nami, Naozumi Ishimaru and Yoshizo Matsuka : Up-regulation of inflammatory cytokines in trigeminal ganglia after infraorbital nerve constriction, The Journal of Neuroscience, Washington DC, Nov. 2017.
11.	Takashi Izawa, Eiji Tanaka and Naozumi Ishimaru : The nuclear receptor AhR controls bone homeostasis by regulating osteoclast differentiation via the RANK/c-Fos signaling axis, ASBMR 2017 Annual Meeting, Denver, Sep. 2017.
12.	Takaaki Tsunematsu, Naozumi Ishimaru and Yasusei Kudo : Chromosome passenger complex protein,Borealin is regulated by APC/C Cdh1 ubiquitin ligase complex, Cold Spring Harbor Laboratory Meeting:The Ubiquitin Family, New York, Apr. 2017.
13.	Takaaki Tsunematsu, Naozumi Ishimaru and Yasusei Kudo : The APC/C-Cdh1-Borealin axis has critical role in the maintenance of undifferentiated state in embryonal carcinoma cells, 8th International Conference SUMO, Ubiquitin, UBL Proteins- Implications for Human Diseases, Shanghai, Oct. 2016.
14.	Akiko Yamada, Aya Ushio, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : Impaired Expansion of Regulatory T cells in a Neonatal Thymectomy-induced Autoimmune Mouse Model, ICI2016, Melbourne, Aug. 2016.
15.	Masako Saito, Kunihiro Ohtsuka, Aya Ushio, Mie Kurosawa, Akiko Yamada, Yasusei Kudo, Rieko Arakaki and Naozumi Ishimaru : Abnormal germinal center(GC)reaction in autoimmunity., ICI2016, Melbourne, Aug. 2016.
16.	Yasusei Kudo, Takaaki Tsunematsu and Naozumi Ishimaru : Chromosome passenger complex protein,Borealin is regulated by APC/C-Cdh1 ubiquitin ligase complex, FASEB Ubiquitin & Cellular Regulation, Montana, Jun. 2016.
17.	Yasusei Kudo, 常松貴明 and Naozumi Ishimaru : Aurora-A controls pre-replicative complex formation and DNA replication by promoting the stabilization of geminin and CDT1 in mitosis., 7th International Conference SUMO,Ubiquitin,UBL Proteins:Implications for Human Diseases, Shanghai, May 2014.
18.	Yasusei Kudo, 常松貴明 and Naozumi Ishimaru : Geminin regulates pre-replicative complex formation though the stabilization of CDT1 in mitosis., American Association for Cancer Reseach, San Diego, Apr. 2014.
19.	Akihiko Iwasa, Rieko Arakaki, Akiko Yamada, Eiji Tanaka, Yasusei Kudo and Naozumi Ishimaru : Pathologenesis of Sjogren's syndrome through Aromatase and adipose tissue., International Congress on Autoimmunity, Niece, Mar. 2014.
20.	Tomoyuki Kondo, Akiko Yamada, Rieko Arakaki, Takaaki Tsunematu, Yasusei Kudo and Naozumi Ishimaru : Analysis of the regulatory mechanism for tumor immunity by using autoimmune lpr mice., International Congress on Autoimmunity, Niece, Mar. 2014.
21.	Koichi Yamada, Akihiko Iwasa, Tomoyuki Kondo, Mie Kurosawa, Rieko Arakaki, Akiko Yamada, Yasusei Kudo, Y Taquahashi, A Takagi, J Kanno and Naozumi Ishimaru : Invivo effect of multi-wall carbon nanotubes on immune system., 6th International Symposium on Nanotechnology,Occupational and Environmental system., Nagoya, Nov. 2013.
22.	Akiko Yamada, Rieko Arakaki, Mie Kurosawa, Tomoyuki Kondo, Koichi Yamada, Yoshio Hayashi and Naozumi Ishimaru : Deficient differentiation of Treg cell in a murine model of Sjogren's syndrome., 15th International Congress of Immunology, Milan, Aug. 2013.
23.	Yosuke Shikama, Naozumi Ishimaru, Yasusei Kudo, Yukiko Bandou, Nanako Aki, Yoshio Hayashi and Makoto Funaki : High Levels of Free Fatty Acids May Advance the Severity of Primary Sjögrens Syndrome, Diabetes, Vol.62, No.Supplement 1, A166, Jul. 2013.
24.	Masahiro Hiasa, Masahiro Abe, Rieko Arakaki, Akiko Yamada, Kenzo Asaoka, Toshio Matsumoto, Yoshio Hayashi and Naozumi Ishimaru : RelB attenuates the activation of the classical NF-κB pathway to facilitate osteoblastogenesis, ANZBMS Annual Scientific Meeting, Perth, Sep. 2012.
25.	Ritsuko 徳永律子 Oura, Akiko Yamada, Rieko Arakaki, Naozumi Ishimaru and Yoshio Hayashi : Pathological Analysis of Autoimmunity in NF-B1KO/LPR mice., 8th International Congress on Autoimmunity, Granada, May 2012.
26.	Akiko Yamada, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : Cathepsin L inhibition prevents murine autoimmune diabetes via suppression of CD8+T cell activity., 8th International Congress on Autoimmunity, Granada, May 2012.
27.	Kazuma Matsumoto, Naozumi Ishimaru, Takashi Izawa, Masahiro Hiasa, Yoshio Hayashi and Eiji Tanaka : Hyperfunctions of osteoclasts in a rheumatoid arthritis model, ASBMR 2011 Annual Meeting, San Diego, Sep. 2011.
28.	Kazuma Matsumoto, Naozumi Ishimaru, Yoshio Hayashi and Eiji Tanaka : Analysis of osteoclast activation in the pathogenesis of rheumatoid arthritis, International Joint Symposium: The University of Tokushima, Universitas Gadjah Mada, Niigata University, Denpasar, Bali, Dec. 2010.
29.	Ashrin Nur Meinar, Naozumi Ishimaru, Megumi Watanabe, Yoshio Hayashi and Tetsuo Ichikawa : Analysis of Molecular Mechanism for Pathogenesis of Metal Allergy, International Joint Symposium, The University of Tokushima-Niigata University-Gajah Mada University, Bali, Dec. 2010.
30.	Naozumi Ishimaru, Akiko Yamada, Rieko Arakaki, Yousuke Takahama and Yoshio Hayashi : Critical Signaling Pathway via CCR7 of Foxp3+CD25+CD4+ Regulatory T Cells for the Egress from Lymph Nodes, international immunology, Aug. 2010.
31.	Kazuma Matsumoto, Naozumi Ishimaru, Takashi Izawa, Rieko Arakaki, Ritsuko 徳永律子 Oura, Eiji Tanaka and Yoshio Hayashi : Fas-independent apoptosis of T cells via DCs controls autoimmune arthritis, international immunology, Vol.22, No.1, 113, Aug. 2010.
32.	Ritsuko 徳永律子 Oura, Naozumi Ishimaru, Rieko Arakaki, Takashi Izawa, Akiko Yamada, Kazuma Matsumoto, Eiji Tanaka and Yoshio Hayashi : Rapid T cell death via interaction with CD11b+ macrophages in Fas-deficient host, international immunology, Vol.22, No.1, 116, Aug. 2010.
33.	Naozumi Ishimaru, Akiko Yamada, Rieko Arakaki, Yousuke Takahama and Yoshio Hayashi : Critical signaling pathway via CCR7 of Foxp3+CD25+CD4+ regulatory T cells for the egress from lymph nodes., 第14回国際免疫学会, Kobe, Aug. 2010.
34.	Ritsuko 徳永律子 Oura, Naozumi Ishimaru, Eiji Tanaka and Yoshio Hayashi : Rapid peripheral T cell death in Fas-deficient mice, 88th IADR, Barcelona, Jul. 2010.
35.	Nao Kinouchi, Emi Kawakami, Yutaka Ohsawa, Naozumi Ishimaru, Hideyo Ohuchi, Yoshihide Sunada, Yoshio Hayashi, Eiji Tanaka and Sumihare Noji : Atelocollagen-mediated Systemic Administration of Myostatin siRNA Improves Muscular Dystrophy, 88th IADR, Barcelona, Jul. 2010.
36.	Emi Kawakami, Nao Kinouchi, Adachi Taro, Yutaka Ohsawa, Naozumi Ishimaru, Hideyo Ohuchi, Yoshihide Sunada, Yoshio Hayashi, Eiji Tanaka and Sumihare Noji : Special Processed Collagen-mediated Application of Myostatin-siRNA for Muscular Atrophy Diseases, 88th IADR, Barcelona, Jul. 2010.
37.	Emi Kawakami, Nao Kinouchi, Yutaka Osawa, Naozumi Ishimaru, Hideyo Ohuchi, Yoshihide Sunada, Yoshio Hayashi, Eiji Tanaka and Sumihare Noji : Strategic study of atelocollagen-mediated application of mystatin-targeting siRNA for therapeutic use for muscular atrophy diseases, QOL International Congress, Niigata, Feb. 2010.
38.	Takeo Iwata, Masamichi Kuwajima, Akiko Sukeno, Naozumi Ishimaru, Yoshio Hayashi, M Wabitsch, Noriko Mizusawa, Mitsuo Itakura and Katsuhiko Yoshimoto : YKL-40 secreted from macrophages infiltrating into adipose tissue inhibits degradation of type I collagen., International symposium on diabetes, Tokyo, Mar. 2009.
39.	Takashi Sakai, Li Liu, Xichuan Teng, Naozumi Ishimaru, Rika Sakai, HoangNam Tran, Nobuya Sano, Yoshio Hayashi, Ryuji Kaji and Kiyoshi Fukui : Inflammatory disease and cancer with a decrease in Kupffer cell numbers in Nucling-konckout mouse, 20th FAOBMB Taipei Conference, Taipei, Oct. 2008.
40.	Nao Kinouchi, Yutaka Osawa, Naozumi Ishimaru, Yoshio Hayashi, Keiji Moriyama, Sumihare Noji and Eiji Tanaka : Atelocollagen-mediated lapplications of myostatin-targeting siRNA increase skeletal muscle mass, 86th IADR, Toronto, Jul. 2008.
41.	Yoshio Hayashi and Naozumi Ishimaru : Development of autoimmune expcrinopathy resembling Sjogren's syndrome in RbAp48 transgenic mice., Boston, Nov. 2007.
42.	Takashi Izawa, Naozumi Ishimaru, Keiji Moriyama and Yoshio Hayashi : Immunoregulatory Role of RANKL-stimulated Dendritic Cells on Autoimmune Arthritis in MRL/lpr Mice, ACR/ARHP 71th Annual Scientific Meeting, Vol.56, No.Suppl 9, S-105, Boston, Nov. 2007.
43.	Yoshio Hayashi and Naozumi Ishimaru : Developmant of autoimmune excrinopathy resembling Sjorgen`s syndrome in RbAp48 transgenic mice., The 71st Annual meeting of the American College of Rheumatology., Bostone,USA., Nov. 2007.
44.	Takashi Izawa, Naozumi Ishimaru, Keiji Moriyama and Yoshio Hayashi : Immunoregulatory role of RANKL-stimulated dendritic cells on autoimmune arthritis in MRL/lpr mice, 29th Annual Meeting of the American Society for Bone and Mineral Research, Vol.22, No.SUPPL 1, S270, Honolulu, Sep. 2007.
45.	Jun Ooshima, Takashi Izawa, Naozumi Ishimaru, Yoshio Hayashi and Keiji Moriyama : Immunoregulatory Effects of Dendritic Cells Stimulated with RANKL on the Development of Autoimmune Disease in Arthritis Model Mice, The 1st International Symposium and Workshop "The Future Direction of Oral Sciences in the 21st Century", 55, Awaji, Mar. 2007.
46.	Naozumi Ishimaru : A novel role of RbAp48 for tissue-specific apoptosis in the salivary glands depending on estrogen deficiency, 第3回ニールスステンセン記念国際唾液腺シンポジウム, Oct. 2006.
47.	Hidehiro Kishimoto, Naozumi Ishimaru and Jonathan Sprent : Regulation of NF-κB1/RelA activation by NF-κB2 in CD4+T cells., The American Association of Immunologist Annual Meeting, Boston, May 2006.
48.	Sprenr Jonathan, Boyman Onur, Cho Hoe Jea, Naozumi Ishimaru and Kovar M : T-Cell Specificity and the Thymus, Scientific Report 2005, Vol.31, 105-107, La Jolla, Jan. 2006.
49.	Yoshio Hayashi and Naozumi Ishimaru : Involvement of Interstitial Pneumonia in Sjogren's Syndrome Mouse Model with Aging., International Symposium on T Cells in Aging., Stuttgart, Dec. 2005.
50.	Yoshio Hayashi, Rieko Arakaki and Naozumi Ishimaru : Possible Mechanism of Autoimmune Exocrinopathy Resembling Sjogren's Syndrome through RbAp48 Overexpression., Gordon Research Conference., Ventura, Feb. 2005.

Proceeding of Domestic Conference:

1.	Rieko Arakaki, Takaaki Tsunematsu, Satoru Kisoda, Naozumi Ishimaru and Aya Ushio : Effect of inhalation exposure to acrbon nanotubes and titanium dioxide on alveolar macrophages, (Keyword) nanoparticle / alveolar macrophage
2.	Kunihiro Otsuka, Hiroyuki Kondo, Shin-ichi Tsukumo, Naozumi Ishimaru and Koji Yasutomo : Salivary gland fibroblasts drive autoimmune pathology via the interaction with CD4+ T cells in Sjögrens syndrome, 第53回日本免疫学会学術集会, Dec. 2024.
3.	NISHIDA Mari, Kunihiro Otsuka, Mami Sato-Fukuba, Kohei Naniwa, Kohichi Kani, Yukihiro Momota, RUKA Nagao, MATSUZAWA Shigefumi, Aya Ushio, Takaaki Tsunematsu, Naozumi Ishimaru and Keiko Aota : シェーグレン症候群における老化関連B細胞の動態と発生機序の検討, 第32回日本シェーグレン症候群学会学術集会, Sep. 2024.
4.	Kunihiro Otsuka, Hiroyuki Kondo, Naozumi Ishimaru and Koji Yasutomo : 線維芽細胞を介した自己免疫病変の増悪機構, 第32回日本シェーグレン症候群学会学術集会, Sep. 2024.
5.	RUKA Nagao, 山本安希子, Aya Ushio, Kunihiro Otsuka, MATSUZAWA Shigefumi, Takaaki Tsunematsu and Naozumi Ishimaru : シェーグレン症候群におけるT Cell Receptor Associated Transmembrane Adaptor 1 (Trat1)を介した活性化T細胞抑制機構の解明, 第22回四国免疫フォーラム, Jun. 2024.
6.	MATSUZAWA Shigefumi, Aya Ushio, RUKA Nagao, Kunihiro Otsuka, TAWARA Hiroaki, Takaaki Tsunematsu and Naozumi Ishimaru : 新生仔の胸腺におけるオートファジーとシェーグレン症候群の関係性, 第113回日本病理学会総会, Mar. 2024.
7.	RUKA Nagao, 山本安希子, Aya Ushio, Kunihiro Otsuka, MATSUZAWA Shigefumi, Takaaki Tsunematsu and Naozumi Ishimaru : シェーグレン症候群の病態形成におけるT細胞の共抑制性受容体役割の解析, 第113回日本病理学会総会, Mar. 2024.
8.	Aya Ushio, Kunihiro Otsuka, Takaaki Tsunematsu, 高橋祐次, 菅野純 and Naozumi Ishimaru : The influence of multi-walled carbon nanotube for immune systems., 第113回日本病理学会総会, Mar. 2024.
9.	富田満, Hidehisa Horiguchi, Hirohisa Ogawa, Hisanori Uehara, Yoshimi Bando, Takaaki Tsunematsu, Mami Sato, Naozumi Ishimaru and Koichi Tsuneyama : CRTC1::MAML2融合遺伝子の検出で確定診断に至った粘表皮癌の2例, 第113回日本病理学会総会, Mar. 2024.
10.	Hiroaki Tawara, Takaaki Tsunematsu, RUKA Nagao, MATSUZAWA Shigefumi, Kunihiro Otsuka, Aya Ushio and Naozumi Ishimaru : Borealin-Survivin複合体は頭頸部扁平上皮癌の分化を直接的に制御する, 第113回日本病理学会総会, Mar. 2024.
11.	Takaaki Tsunematsu, Harunori Yoshikawa, RUKA Nagao, MATSUZAWA Shigefumi, Kunihiro Otsuka, Aya Ushio and Naozumi Ishimaru : がん特殊化リボソームの同定と機能解析, 第113回日本病理学会総会, Mar. 2024.
12.	RUKA Nagao, Takaaki Tsunematsu, MATSUZAWA Shigefumi, Kunihiro Otsuka, Aya Ushio and Naozumi Ishimaru : 下顎骨腫瘍, 第143回日本病理学会中国四国支部学術集会, Feb. 2024.
13.	MATSUZAWA Shigefumi, Takaaki Tsunematsu, RUKA Nagao, Kunihiro Otsuka, Aya Ushio, Takeshi Oya and Naozumi Ishimaru : 歯肉腫瘍, 日本病理学会中国四国支部学術集会(第143回スライドカンファレンス), Feb. 2024.
14.	MATSUZAWA Shigefumi, Aya Ushio, RUKA Nagao, Kunihiro Otsuka, TAWARA Hiroaki, Takaaki Tsunematsu and Naozumi Ishimaru : 新生仔胸腺におけるT細胞の分化・成熟とオートファジーの関連についての検討, 2023年度感染・免疫クラスター・ミニリトリート, Feb. 2024.
15.	MATSUZAWA Shigefumi, Aya Ushio, RUKA Nagao, TAWARA Hiroaki, Kunihiro Otsuka, Takaaki Tsunematsu and Naozumi Ishimaru : Investigation of the relationship between T cell differation and autophagy in the neonatal thymus., 第52回日本免疫学会総会・学術集会, Jan. 2024.
16.	RUKA Nagao, 山本安希子, Aya Ushio, Kunihiro Otsuka, TAWARA Hiroaki, MATSUZAWA Shigefumi, Kai Tamura, KAWAHITO Yuki, Takaaki Tsunematsu and Naozumi Ishimaru : Analysis of the suppression mechanism for activated T cells via co-inhibitory receptors in Sjogrens syndrome, 第52回日本免疫学会総会・学術集会, Jan. 2024.
17.	Kai Tamura, KAWAHITO Yuki, Mami Sato, Kunihiro Otsuka, Aya Ushio, Takaaki Tsunematsu and Naozumi Ishimaru : Pathological analysis of nasal lesions with aging in murine models of Sjögrens syndrome, 第52回日本免疫学会総会・学術集会, Jan. 2024.
18.	KAWAHITO Yuki, Tamura Kai, Mami Sato, Kunihiro Otsuka, Aya Ushio, Takaaki Tsunematsu and Naozumi Ishimaru : The Relation between the Reduction of Mucin 19 and the Onset of Sjögrens syndrome in a Mouse Model, 第52回日本免疫学会総会・学術集会, Jan. 2024.
19.	Takaaki Tsunematsu, RUKA Nagao, MATSUZAWA Shigefumi, Kunihiro Otsuka, Aya Ushio and Naozumi Ishimaru : The molecular mechanism of Cancer cell cannibalism and its significance in cancer progression, 第52回日本免疫学会総会・学術集会, Jan. 2024.
20.	Kunihiro Otsuka, Hiroyuki Kondo, Shin-ichi Tsukumo, Aya Ushio, Naozumi Ishimaru and Koji Yasutomo : CD153+ CD4+ T cells and CD30+ cells exacerbate the autoimmune pathology in salivary glands of Sjögren's syndrome, 第52回日本免疫学会学術集会, Jan. 2024.
21.	富田満, Hidehisa Horiguchi, Takaaki Tsunematsu, Naozumi Ishimaru and Koichi Tsuneyama : 顎下腺腫瘍, 日本病理学会中国四国支部学術集会(第142回スライドカンファレンス, Nov. 2023.
22.	Takaaki Tsunematsu, TAWARA Hiroaki and Naozumi Ishimaru : DNA損傷シグナルによってがん細胞が獲得する新たな機能, 第59回日本口腔組織培養学会総会・学術大会, Nov. 2023.
23.	Hiroaki Tawara, Takaaki Tsunematsu, Kunihiro Otsuka, Aya Ushio and Naozumi Ishimaru : 口腔扁平上皮癌におけるSurvivinの核内蓄積がもたらす新たな機能, 第59回日本口腔組織培養学会総会・学術大会, Nov. 2023.
24.	Aya Ushio, 松田真美, Naozumi Ishimaru and Yousuke Takahama : 機能的に異なる髄質胸腺上皮サブセットが中枢性自己寛容確立にもたらす相互作用, 第69回日本病理学会秋期特別総会, Nov. 2023.
25.	MATSUZAWA Shigefumi, Aya Ushio, RUKA Nagao, Kunihiro Otsuka, TAWARA Hiroaki, Takaaki Tsunematsu and Naozumi Ishimaru : シェーグレン症候群と胸腺におけるT細胞の分化・成熟の関連についての検討, 第31回日本シェーグレン症候群学会学術集会, Sep. 2023.
26.	Kunihiro Otsuka, Hiroyuki Kondo, Shin-ichi Tsukumo, Aya Ushio, RUKA Nagao, Keiko Aota, Naozumi Ishimaru and Koji Yasutomo : シングルセル解析を基盤としたシェーグレン症候群の病態解明, 第31回日本シェーグレン症候群学会学術集会, Sep. 2023.
27.	Jin Shengjian, Takaaki Tsunematsu, Taigo Horiguchi, Yasuhiro Mouri, Wenhua Shao, Keiko Miyoshi, Noriko Mizusawa, Hagita Hiroko, Sarubo Motoharu, Yoshida Kayo, Kaya Yoshida, Natsumi Fujiwara, Kazumi Ozaki, Naozumi Ishimaru and Yasusei Kudo : The role of deubiquitinating enzyme, OTUB1 in head and neck squamous cell carcinoma (HNSCC) progression, 第82回日本癌学会学術集会, Sep. 2023.
28.	Aya Ushio, 松田真美, Naozumi Ishimaru and Yousuke Takahama : 中枢性自己寛容確立に関わる機能的に異なる髄質胸腺上皮サブセットの相互作用, 第65回歯科基礎医学会学術大会, Sep. 2023.
29.	TAWARA Hiroaki, Takaaki Tsunematsu, Kunihiro Otsuka, Aya Ushio and Naozumi Ishimaru : 頭頚部扁平上皮癌における染色体パッセンジャー複合体非依存的なBorealin-Survivin相互作用がもたらす新たな機能, 第65回歯科基礎医学会学術大会, Sep. 2023.
30.	Takaaki Tsunematsu and Naozumi Ishimaru : ``がんの共食い``の分子機構とその生物学的意義の解明, 2023年度徳島大学先端酵素学研究所シンポジウム, Sep. 2023.
31.	TAWARA Hiroaki, Takaaki Tsunematsu, RUKA Nagao, MATSUZAWA Shigefumi, Aya Ushio, Kunihiro Otsuka and Naozumi Ishimaru : Novel role of nuclear Survivin in head and neck squamous carcinoma, 2023 Tokushima Bioscience Retreat, Sep. 2023.
32.	TAWARA Hiroaki, Takaaki Tsunematsu, RUKA Nagao, MATSUZAWA Shigefumi, Kunihiro Otsuka, Aya Ushio and Naozumi Ishimaru : 染色体パッセンジャー複合体構成因子Borealin-Survivin相互作用は頭頚部扁平上皮癌の代謝を制御する, 第34回日本臨床口腔病理学会総会・学術大会, Aug. 2023.
33.	Takaaki Tsunematsu and Naozumi Ishimaru : ``がんの共食い''の分子機構とその生物学的意義の解明, 第40回分子病理学研究会, Jul. 2023.
34.	Kunihiro Otsuka, Naozumi Ishimaru and Koji Yasutomo : CD153+ CD4+ T cellによるシェーグレン症候群の新たな発症機序の解明, 第5回口腔医科学フロンティア研究会, Apr. 2023.
35.	Kai Tamura, Yuki KAWAHITO, Mami Sato, Kunihiro Otsuka, Takaaki Tsunematsu and Naozumi Ishimaru : シェーグレン症候群モデルマウスにおける加齢に伴う鼻腔病変の病態解析, 第112回日本病理学会総会, Apr. 2023.
36.	Yuki KAWAHITO, Kai Tamura, Mami Sato, Kunihiro Otsuka, Takaaki Tsunematsu and Naozumi Ishimaru : シェーグレン症候群疾患モデルマウスにおけるMucin19の異常と病態との関連性の解析, 第112回日本病理学会総会, Apr. 2023.
37.	Takaaki Tsunematsu, Hiroaki TAWARA, Mami Sato, Kazuki FUKUTA, Kunihiro Otsuka, Aya Ushio and Naozumi Ishimaru : DNA損傷シグナルによって誘導されるがん細胞の新たな機能とその分子機構, 第112回日本病理学会総会, Apr. 2023.
38.	Hiroaki TAWARA, Takaaki Tsunematsu, Kazuki FUKUTA, RUKA Nagao, Mami Sato, Kunihiro Otsuka, Aya Ushio and Naozumi Ishimaru : 染色体パッセンジャー複合体構成因子Borealin-Survivin相互作用は頭頸部扁平上皮癌の代謝を制御する, 第112回日本病理学会総会, Apr. 2023.
39.	RUKA Nagao, 山本安希子, Kunihiro Otsuka, Aya Ushio, TAWARA Hiroaki, TANAKA Hidetaka, Kunihiro Otsuka, Takaaki Tsunematsu and Naozumi Ishimaru : T細胞の共抑制性受容体を介したシェーグレン症候群の発症機序の解析, 第112回日本病理学会総会, Apr. 2023.
40.	Aya Ushio, 松田-Lennikov 真実, Kunihiro Otsuka, Takaaki Tsunematsu, Naozumi Ishimaru and Yousuke Takahama : 自己免疫疾患発症における多様性胸腺髄質上皮細胞の相乗的制御機構, 第112回日本病理学会総会, Apr. 2023.
41.	Kunihiro Otsuka, Hiroyuki Kondo, Shin-ichi Tsukumo, Rieko Arakaki, Ruka Nagao, Mami Sato, Aya Ushio, Naozumi Ishimaru and Koji Yasutomo : CD153-CD30相互反応を介したシェーグレン症候群の病態形成機構の解明, 第112回日本病理学会総会, Apr. 2023.
42.	Jin Shengjian, Takaaki Tsunematsu, Taigo Horiguchi, Yasuhiro Mouri, Wenhua Shao, Keiko Miyoshi, Noriko Mizusawa, Hiroko Hagita, YOSHIDA Kayo, Kaya Yoshida, Natsumi Fujiwara, Kazumi Ozaki, Naozumi Ishimaru and Yasusei Kudo : The role of Deubiquitinating enzyme, OTUB1 in head and neck squamous cell carcinoma (HNSCC) progression, 第61回四国歯学会, Mar. 2023.
43.	Takaaki Tsunematsu, TAWARA Hiroaki and Naozumi Ishimaru : HPV陽性癌における新規脱ユビキチン化酵素複合体の分子機構の解明, 第58回日本口腔組織培養学会学術大会・総会, Dec. 2022.
44.	Hiroaki TAWARA, Takaaki Tsunematsu, Nagao RUKA, Kazuki FUKUTA, Mami Sato, Kunihiro Otsuka, Aya Ushio and Naozumi Ishimaru : 頭頸部扁平上皮癌における染色体パッセンジャー複合体構成因子Borealinの高発現がもたらす新たな役割, 第58回日本口腔組織培養学会学術大会・総会, Dec. 2022.
45.	Mami Sato, Aya Ushio, Kunihiro Otsuka, Takaaki Tsunematsu and Naozumi Ishimaru : Th2 response enhances the differentiation into follicular B cells to progress the pulmonary autoimmune lesions in a mouse model of Sjögrens syndrome, 第51回日本免疫学会学術集会, Dec. 2022.
46.	Kunihiro Otsuka, Shin-ichi Tsukumo, Rieko Arakaki, Mami Sato, 八木田秀雄, Naozumi Ishimaru and Koji Yasutomo : CD153+ CD4+ T cells exacerbate the autoimmune pathology via the interaction with CD30+ cells in salivary glands in Sjögren's syndrome., 第51回日本免疫学会学術集会, Dec. 2022.
47.	Kai Tamura, Yuki KAWAHITO, Mami Sato, Kunihiro Otsuka, Takaaki Tsunematsu and Naozumi Ishimaru : Pathological analysis of nasal tissue in a murine model of Sjögrens syndrome, 第51回日本免疫学会学術集会, Dec. 2022.
48.	Yuki KAWAHITO, Kai Tamura, Mami Sato, Kunihiro Otsuka, Takaaki Tsunematsu and Naozumi Ishimaru : Role of Mucin 19 in Pathogenesis of a Mouse Model for Sjögren's Syndrome, 第51回日本免疫学会学術集会, Dec. 2022.
49.	Takaaki Tsunematsu, Rieko Arakaki, Mami Sato, Kunihiro Otsuka and Naozumi Ishimaru : Exposure to Multi-Wall Carbon Nanotubes Promotes Fibrous Proliferation by Production of Matrix Metalloproteinase-12 via NF-κB Activation in Chronic Peritonitis, 第51回日本免疫学会学術集会, Dec. 2022.
50.	RIN Fukuike, 月本準, Yuto Horii, Yoshie Takeuchi, Nijiho Kamori, Mizuki Miyoshi, 木野倫子, Naozumi Ishimaru and Kouji Itou : AAVPHP.eBベクターの脳室内単回投与によるNEU1⽋損症に対する遺伝⼦治療, 第45回日本分子生物学会年会, Dec. 2022.
51.	Mizuki Miyoshi, 月本準, Yuto Horii, Yoshie Takeuchi, Nijiho Kamori, RIN Fukuike, 木野倫子, Naozumi Ishimaru and Kouji Itou : 効率的治療を⽬的としたリソソーム性ノイラミニダーゼ1⽋損症に対するAAV5遺伝⼦治療, 第45回日本分子生物学会年会, Dec. 2022.
52.	Hiroaki TAWARA, Takaaki Tsunematsu, RUKA Nagao, Mami Sato, Kunihiro Otsuka and Naozumi Ishimaru : がんにおける染色体パッセンジャー複合体構成因子Borealinの高発現がもたらす新たな機能, 第45回日本分子生物学学会年会, Dec. 2022.
53.	Takaaki Tsunematsu and Naozumi Ishimaru : Cell Cycle machinery unravels the molecular mechanism of Cancer cell cannibalism, 第45回日本分子生物学学会年会, Nov. 2022.
54.	Mizuki Miyoshi, 月本準, Yuto Horii, Yoshie Takeuchi, Nijiho Kamori, RIN Fukuike, 木野倫子, Naozumi Ishimaru and Kouji Itou : 先天代謝異常症ガラクトシアリドーシスに対するより効果的な遺伝子治療薬開発, 第95回日本生化学会大会, Nov. 2022.
55.	Naoyuki Fukuda, Natsumi Takamaru, Kazuya Akita, Keiko Kudoh, Takaaki Tsunematsu, Naozumi Ishimaru and Youji Miyamoto : 超選択的動脈塞栓術を併用して治療した上顎中心性巨細胞肉芽腫の1例, 第67回日本口腔外科学会総会・学術大会, Nov. 2022.
56.	Kunihiro Otsuka, Hiroyuki Kondo, Shin-ichi Tsukumo, Rieko Arakaki, Mami Sato, Takaaki Tsunematsu, Naozumi Ishimaru and Koji Yasutomo : シングルセルRNA-seqとマルチプレックスSpatial解析を基盤としたシェーグレン症候群の標的臓器微小環境変化の解明, 第33回日本臨床口腔病理学会, Sep. 2022.
57.	Naozumi Ishimaru : 唾液腺免疫難病研究の最前線, 第33回日本臨床口腔病理学会学術大会シンポジウム, Sep. 2022.
58.	Takaaki Tsunematsu, Hiroaki TAWARA, Mami Sato, Rieko Arakaki, Kunihiro Otsuka, Aya Ushio and Naozumi Ishimaru : 頭頸部扁平上皮癌における染色体パッセンジャー複合体構成因子Borealinの新たな機能, 第64回歯科基礎医学会学術大会, Sep. 2022.
59.	Yuki KAWAHITO, Kai Tamura, Mami Sato, Kunihiro Otsuka, Takaaki Tsunematsu and Naozumi Ishimaru : シェーグレン症候群モデルマウスであるNFS/sldマウスの変異遺伝子Mucin19の発現解析と病態との関連性, 第64回歯科基礎医学会学術大会, Sep. 2022.
60.	Kunihiro Otsuka, Shin-ichi Tsukumo, Hiroyuki Kondo, Mami Sato, Hiroaki TAWARA, Takaaki Tsunematsu, Naozumi Ishimaru and Koji Yasutomo : シングルセルRNA-seqで紐解くシェーグレン症候群モデルに特徴的に出現するT細胞集団の解析, 第64回歯科基礎医学会学術大会, Sep. 2022.
61.	Kai Tamura, Yuki KAWAHITO, Mami Sato, Kunihiro Otsuka, Takaaki Tsunematsu and Naozumi Ishimaru : シェーグレン症候群モデルマウスにおける鼻腔組織の病態解析, 第64回歯科基礎医学会学術大会, Sep. 2022.
62.	Mami Sato, Aya Ushio, Kunihiro Otsuka, Takaaki Tsunematsu and Naozumi Ishimaru : シェーグレン症候群モデルマウス肺病変におけるケモカインの機能分析, 第64回歯科基礎医学会学術大会, Sep. 2022.
63.	shengjian jin, Takaaki Tsunematsu, Taigo Horiguchi, Naozumi Ishimaru and Yasusei Kudo : 脱ユビキチン化酵素OTUB1の頭頸部扁平上皮癌の進展における役割, 第64回歯科基礎医学会学術大会, Sep. 2022.
64.	Mami Sato, Aya Ushio, Kunihiro Otsuka, Takaaki Tsunematsu and Naozumi Ishimaru : シェーグレン症候群疾患モデルマウスの肺病変における濾胞B細胞の自己反応性獲得機構の解明, 先端歯学国際教育研究ネットワーク先端歯学スクール, Aug. 2022.
65.	Takaaki Tsunematsu and Naozumi Ishimaru : 頭頚部扁平上皮癌における染色体パッセンジャー複合体構成因子Borealinの新たな機能, 第39回分子病理研究会内灘かほくシンポジウム, Jul. 2022.
66.	Mami Sato, Aya Ushio, Kazuki FUKUTA, Hiroaki TAWARA, Kunihiro Otsuka, Takaaki Tsunematsu, Rieko Arakaki and Naozumi Ishimaru : Extraglandular lesions in Sjogren's syndorome model mice., 第20回四国免疫フォーラム, Jun. 2022.
67.	Mami Sato, Aya Ushio, Kunihiro Otsuka, Takaaki Tsunematsu, Rieko Arakaki and Naozumi Ishimaru : シェーグレン症候群モデルマウス肺病変に対するケモカイン群の機能的解析, 第20回四国免疫フォーラム, Jun. 2022.
68.	Takaaki Tsunematsu and Naozumi Ishimaru : 口腔扁平上皮癌におけるchromosome passenger complex構成因子Borealinが誘導するSurvivin安定化機構の解明, 第76回日本口腔科学会学術集会, Apr. 2022.
69.	Keiko Aota, Kohichi Kani, Yukihiro Momota, Naozumi Ishimaru and Masayuki Azuma : シェーグレン症候群唾液腺におけるJAKsの発現解析, 第76回日本口腔科学会学術集会, Apr. 2022. (Keyword) Sjögren's syndrome / JAK
70.	Kai Tamura, Rieko Arakaki and Naozumi Ishimaru : シェーグレン症候群モデルマウス鼻腔組織の病態解析, 第111回日本病理学会総会, Apr. 2022.
71.	Takaaki Tsunematsu, Hiroaki TAWARA, Hidetaka TANAKA, Kazuki FUKUTA, Mami Sato, Kunihiro Otsuka, Rieko Arakaki and Naozumi Ishimaru : 口腔扁平上皮癌におけるBorealinの高発現がもたらすSurvivin安定化機構の解明, 第111回日本病理学会総会, Apr. 2022.
72.	Kunihiro Otsuka, Shin-ichi Tsukumo, Hiroyuki Kondo, Rieko Arakaki, Naozumi Ishimaru and Koji Yasutomo : シングルセルRNA-seqで紐解くシェーグレン症候群モデルに特徴的に出現するT細胞集団の解析, 第111回日本病理学会総会, Apr. 2022.
73.	Mami Sato, Rieko Arakaki, Takaaki Tsunematsu, Yasusei Kudo and Naozumi Ishimaru : シェーグレン症候群疾患モデルにおける肺病変発症へのCCL6の役割, 第111回日本病理学会総会, Apr. 2022.
74.	Mami Sato, Takaaki Tsunematsu, Kunihiro Otsuka and Naozumi Ishimaru : 下顎骨病変, 日本病理学会中国四国支部学術集会 (第 137 回スライドカンファレンス), Feb. 2022.
75.	Rieko Arakaki, Takaaki Tsunematsu and Naozumi Ishimaru : Pulmonary immune response and molecular mechanism of fibrosis by inhalation exposure to nanomaterials, 第50回日本免疫学会学術集会, Dec. 2021.
76.	Kunihiro Otsuka, Shin-ichi Tsukumo, Rieko Arakaki, Mami Sato, Hideo Yagita, Naozumi Ishimaru and Koji Yasutomo : Single-cell RNA sequencing reveals accumulation of CD4 and CD8 T cells with unique phenotypes in salivary glands of Sjögren's syndrome model mice, 第50回日本免疫学会学術集会, Dec. 2021.
77.	Keiko Aota, Kohichi Kani, Yukihiro Momota, Naozumi Ishimaru and Masayuki Azuma : シェーグレン症候群唾液腺におけるJAK1およびJAK2の発現解析, 第66回日本口腔外科学会学術集会, Nov. 2021.
78.	Takaaki Tsunematsu, Rieko Arakaki and Naozumi Ishimaru : HPV陽性癌細胞の増殖に必須の脱ユビキチン化酵素の同定とその分子メカニズムの解明, 第57回口腔組織培養学会学術大会, Nov. 2021.
79.	Takaaki Tsunematsu and Naozumi Ishimaru : がん細胞の老化細胞様変化による新たな機能の獲得とその分子機構, 第63回歯科基礎医学会学術大会アップデートシンポジウム「がん研究の新たな潮流~歯学基礎研究からの発信~」, Oct. 2021.
80.	Naozumi Ishimaru : 基礎歯学研究の進化と展望, 第63回歯科基礎医学会先端歯学国際教育研究ネットワークシンポジウム, Oct. 2021.
81.	俵宏彰, Rieko Arakaki, Kunihiro Otsuka and Naozumi Ishimaru : シェーグレン症候群モデルマウスを用いたM3PAMを用いた治療効果とその作用機序, 第29回日本シェーグレン症候群学会学術集会, Sep. 2021.
82.	田村海, Rieko Arakaki, 太田康 and Naozumi Ishimaru : シェーグレン症候群モデルマウスを用いたドライノーズ病態の解析, 第29回日本シェーグレン症候群学会学術集会, Sep. 2021.
83.	Mami Sato, 牛尾綾, 福田一稀, 俵宏彰, Kunihiro Otsuka, Takaaki Tsunematsu, Rieko Arakaki and Naozumi Ishimaru : シェーグレン症候群モデルマウスにおける肺病変の病態探索, 第29回日本シェーグレン症候群学会学術集会, Sep. 2021.
84.	Kunihiro Otsuka, Akiko Yamada, Masako Saito, Aya Ushio, Mami Sato, Satoru Kisoda, Wenhua Shao, Takaaki Tsunematsu, Yasusei Kudo, Rieko Arakaki and Naozumi Ishimaru : Achaete-Scute Homologue 2-Regulated Follicular Helper T Cells Promote Autoimmunity in a Murine Model for Sjögren Syndrome., 第32回日本臨床口腔病理学会奨励賞(実験病理分野), Aug. 2021.
85.	長友涼介, Mayuko Shimizu, Koichi Tsuneyama, Naozumi Ishimaru and 井之上浩一 : 誘導体化LC-MS/MSによる網羅的短鎖脂肪酸解析: モデルマウス病態への応用, 第 6 回日本医用マススペクトル学会西部会, Jul. 2021.
86.	Naozumi Ishimaru, Rieko Arakaki, Takaaki Tsunematsu, 高橋祐次 and 菅野純 : ナノマテリアルの吸入暴露による肺免疫応答と線維化の分子機構, 第48回日本毒性学会学術年会, Jul. 2021.
87.	Naozumi Ishimaru : 口腔科学を牽引する基礎研究の展望, 日本補綴歯科学会第130回記念学術大会シンポジウム, Jun. 2021.
88.	Mami Sato, Aya Ushio, Kazuki FUKUTA, Hiroaki TAWARA, Kunihiro Otsuka, Takaaki Tsunematsu, Rieko Arakaki and Naozumi Ishimaru : シェーグレン症候群モデルマウスにおける腺外病変, 第19回四国免疫フォーラム, Jun. 2021.
89.	Takaaki Tsunematsu, KITAGAWA Takumi, Yasusei Kudo and Naozumi Ishimaru : 口腔扁平上皮癌の進展におけるPeriostinスプライシングバリアントの新たな役割, 第75回日本口腔科学会学術集会, May 2021.
90.	Mami Sato, 牛尾綾, Takaaki Tsunematsu, Rieko Arakaki and Naozumi Ishimaru : シェーグレン症候群モデルマウスにおける肺病変の解析, 第110回日本病理学会学術集会, Apr. 2021.
91.	Rieko Arakaki, 清水朱里, Mami Sato, 俵宏彰, Takaaki Tsunematsu and Naozumi Ishimaru : 唾液腺における常在型自然リンパ球の同定とシェーグレン症候群病態への関与, 第110回日本病理学会学術集会, Apr. 2021.
92.	Takaaki Tsunematsu, Takumi KITAGAWA, Mami Sato, Rieko Arakaki and Naozumi Ishimaru : HPV陽性扁平上皮癌細胞の生存に必須な脱ユビキチン化酵素の同定とその役割の解明, 第110回日本病理学会総会, Apr. 2021.
93.	Mami Sato, Aya Ushio, Rieko Arakaki, 俵宏彰, Takaaki Tsunematsu and Naozumi Ishimaru : シェーグレン症候群モデルマウスにおける腺外病変の発症機序, 四国歯学会第57回例会, Mar. 2021.
94.	Mami Sato, Takaaki Tsunematsu, Kunihiro Otsuka and Naozumi Ishimaru : 下顎骨病変, 日本病理学会中国四国支部学術集会第 137 回スライドカンファレンス, Feb. 2021.
95.	Kisoda Satoru, Wenhua Shao, Jin Shengjian, Takaaki Tsunematsu, Naozumi Ishimaru and Yasusei Kudo : Development of a novel prognostic prediction system for head and neck squamous cell carcinoma, 第79回日本癌学会学術総会, Oct. 2020.
96.	Takaaki Tsunematsu, Yasusei Kudo and Naozumi Ishimaru : 多角的アプローチによる口腔癌の発生・進展の分子機構の解明, 第62回歯科基礎医学会学術大会先端歯学国際教育研究ネットワーク・シンポジウム「歯学研究の今昔と次世代研究」, Sep. 2020.
97.	Naozumi Ishimaru : シェーグレン症候群モデルマウスにおける肺病変の解析, 第62回歯科基礎医学会学術大会, Sep. 2020.
98.	Naozumi Ishimaru : シェーグレン症候群の標的臓器におけるIL-33の役割, 第109回日本病理学会総会, Jul. 2020.
99.	Naozumi Ishimaru : 口腔腫瘍の病理と遺伝子異常―癌形質と微小環境―オーバービュー/, 第109回日本病理学会総会, Jul. 2020.
100.	Naozumi Ishimaru : 多層化カーボンナノチューブと酸化チタン吸入暴露による肺胞マクロファージの動態, 第109回日本病理学会総会, Jul. 2020.
101.	Wenhua Shao, Umeda Masaaki, Takaaki Tsunematsu, Kisoda Satoru and Naozumi Ishimaru : Novel periostin inform promotes invasion and metastasis in head and neck squamous cell carcinoma., 第109回日本病理学会総会, Jul. 2020.
102.	Takaaki Tsunematsu, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : 染色体パッセンジャー複合体による胎児性癌の未分化性維持機構, 第109回日本病理学会総会, Jul. 2020.
103.	Naito Kurio, Kumiko Kamada, 横田美保, Yoshiko Yamamura, Aya Ushio, Yasusei Kudo, Naozumi Ishimaru and Youji Miyamoto : 上顎歯肉に発生した微小嚢胞性付属器癌の1例, 第38回日本口腔腫瘍学会総会・学術大会, Jan. 2020.
104.	Yoshiko Yamamura, Go Ohe, Yasusei Kudo, Naito Kurio, 鎌田久美子, Naoyuki Fukuda, Keiko Kudoh, Takamitsu Mano, Naozumi Ishimaru and Youji Miyamoto : 口腔扁平苔癬からの癌化が疑われた口腔扁平上皮癌の4例, 第38回日本口腔腫瘍学会総会・学術大会, Jan. 2020.
105.	Kumiko Kamada, Naito Kurio, Go Ohe, Keiko Kudoh, Yasusei Kudo, Takamitsu Mano, Naozumi Ishimaru and Youji Miyamoto : 口底に発生した類基底扁平上皮癌の1例, 第38回日本口腔腫瘍学会総会・学術大会, Jan. 2020.
106.	Aya Ushio, Rieko Arakaki, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : Analysis of pulmonary lesions in a murlne model of sjogren's syndorome., Proceedings of the Japanese Society for Immunology, Dec. 2019.
107.	Mami Sato, Rieko Arakaki, Aya Ushio, Yasusei Kudo and Naozumi Ishimaru : Effect of mulyi-wall carbon nanotube exposure on pulmonary immune cells at the early stage., Proceedings of the Japanese Society for Immunology, Dec. 2019.
108.	Kumiko Kamada, Naito Kurio, Go Ohe, Keiko Kudoh, Yoshiko Yamamura, Naoyuki Fukuda, Takamitsu Mano, Yasusei Kudo, Naozumi Ishimaru and Youji Miyamoto : 上顎歯肉に発生したMicorocystic adnexal carcinoma(MAC)の1例, 第64回日本口腔外科学会総会・学術大会, Oct. 2019.
109.	Aya Ushio, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : 自己免疫疾患モデルにおける標的臓器常在型マクロファージの役割, Japanese Journal of Oral Biology, Oct. 2019.
110.	Naito Kurio, 鎌田久美子, Go Ohe, 横田美保, Yoshiko Yamamura, Keiko Kudoh, Yasusei Kudo, Takamitsu Mano, Naozumi Ishimaru and Youji Miyamoto : 歯肉腫瘤により白血病化が明らかとなった骨髄異形成症候群の1例, 第67回日本口腔科学会中国・四国地方部会, Oct. 2019.
111.	鎌田久美子, Naito Kurio, Go Ohe, Yoshiko Yamamura, Keiko Kudoh, Yasusei Kudo, Naozumi Ishimaru and Youji Miyamoto : 口底に発生した類基底扁平上皮癌の1例, 第18回中四国口腔癌研究会, Oct. 2019.
112.	Satoru Kisoda, Bunka Sho, Takaaki Tsunematsu, Naozumi Ishimaru and Yasusei Kudo : 口腔癌におけるpartial EMTに関連する遺伝子の悪性度への関与, 第78回日本癌学会学術総会, Sep. 2019.
113.	Satoru Kisoda, Wenhua Shao, Takaaki Tsunematsu, Naozumi Ishimaru and Yasusei Kudo : 口腔癌におけるpartial-EMTに関連する遺伝子の悪性度への関与, 第78回日本癌学会学術総会, Sep. 2019.
114.	Keiko Aota, Tomoko Yamanoi, Kohichi Kani, Naozumi Ishimaru and Masayuki Azuma : シェーグレン症候群の病態形成におけるCXCL10-CXCR3の役割, 第28回日本シェーグレン症候群学会, Sep. 2019.
115.	Aya Ushio, Rieko Arakaki, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : The new therapeutic strategy targeting chemokine in Sjogren's Syndorome., 日本RNAi研究会, Aug. 2019.
116.	Takaaki Tsunematsu, Naozumi Ishimaru and Yasusei Kudo : The maintenance of pluripotency by chromosome passenger complex in pluripotent stem cells., 日本RNAi研究会, Aug. 2019.
117.	Takaaki Tsunematsu, Naozumi Ishimaru and Yasusei Kudo : 染色体パッセンジャー複合体によるAurora-B活性を介した多能性幹細胞の未分化能維持機構, 第16回日本病理学会カンファレンス, Aug. 2019.
118.	Satoru Kisoda, Wenhua Shao, Aya Ushio, Mami Sato, Rieko Arakaki, Naozumi Ishimaru and Yasusei Kudo : 口腔癌におけるpartial-EMTに関する遺伝子の悪性度への関与, 第38回分子病理研究会, Jul. 2019.
119.	Aya Ushio, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : シェーグレン症候群モデルマウスの唾液腺病態形成におけるマクロファージの役割, 第38回分子病理研究会, Jul. 2019.
120.	Takaaki Tsunematsu, Naozumi Ishimaru and Yasusei Kudo : 染色体パッセンジャー複合体による未分化能維持機構, 第135回日本薬理学会近畿部会, Jun. 2019.
121.	Aya Ushio, Rieko Arakaki, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : シェーグレン症候群モデルマウスの標的組織マクロファージが病態形成に及ぼす影響, 第18回四国免疫フォーラム, Jun. 2019.
122.	Tomoko Yamanoi, Keiko Aota, Hideyuki Takano, Kohichi Kani, Yukihiro Momota, Fumihiro Matsumoto, Naozumi Ishimaru and Masayuki Azuma : 舌下-オトガイ下型類皮嚢胞の一例, 第48回日本口腔外科学会中四国支部学術集会, May 2019.
123.	Haruna Matsukura, Aya Ushio, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : シェーグレン症候群疾患モデルにおける胚病変の解析, 第108回日本病理学会総会, May 2019.
124.	Aya Ushio, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : シェーグレン症候群病態形成におけるCCL22産生マクロファージの役割, 第108回日本病理学会総会, May 2019.
125.	Keiko Aota, Tomoko Yamanoi, Kohichi Kani, Naozumi Ishimaru and Masayuki Azuma : シェーグレン症候群の病態形成におけるCXCL10-CXCR3の役割, 第73回日本口腔科学会学術集会, Apr. 2019.
126.	Takaaki Tsunematsu, Hidehiko Kawai, Naozumi Ishimaru, Willium C Earnshaw, Michele Pagano and Yasusei Kudo : 染色体パッセンジャー複合体による多能性幹細胞の未分化能維持機構, 第36回染色体ワークショップ, Jan. 2019. (Keyword) cell cycle / induced pluripotent stem cells
127.	Rieko Arakaki, Nakayama Shinichiro, Aya Ushio, Otsuka Kunihiro, Kisoda Satoshi, Takaaki Tsunematsu, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : The role of the cleaved from IL-33 in pathogenesis of Sjogren's syndorome(SS), Proceedings of the Japanese Society for Immunology, Dec. 2018.
128.	Aya Ushio, Rieko Arakaki, Kunihiro Ohtsuka, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : CCL22-producing macrophages promote T cell autoimmunity in the target organ of Sjogren's syndorome., Proceedings of the Japanese Society for Immunology, Dec. 2018.
129.	Kunihiro Ohtsuka, Akiko Yamada, Masako Saito, Aya Ushio, Satoru Kisoda, Takaaki Tsunematsu, Yasusei Kudo, Rieko Arakaki and Naozumi Ishimaru : A crucial role of follicular helper T cells in autoimmunity of a mouse model for Sjogren's syndorome., Proceedings of the Japanese Society for Immunology, Dec. 2018.
130.	Takaaki Tsunematsu, Naozumi Ishimaru and Yasusei Kudo : 多能性幹細胞においてAPC/CCdh1によるBorealinの分解は分化を誘発する, 第41回日本分子生物学会年会, Nov. 2018. (Keyword) cell cycle / induced pluripotent stem cells
131.	榊原健人, Takayuki Nakagawa, Naoyuki Fukuda, Naito Kurio, Tetsuya Tamatani, Takamitsu Mano, 大塚邦紘, Yasusei Kudo, Naozumi Ishimaru and Youji Miyamoto : 下顎骨に発生した腺性歯原性嚢胞の1例, 第66回日本口腔科学会中国・四国地方部会, Nov. 2018.
132.	Kunihiro Ohtsuka, Akiko Yamada, Masako Saito, Aya Ushio, Satoru Kisoda, Takaaki Tsunematsu, Yasusei Kudo, Rieko Arakaki and Naozumi Ishimaru : シェーグレン症候群疾患モデルの自己免疫病変における濾胞ヘルパーT細胞の役割, 日本シェーグレン症候群学会, Sep. 2018.
133.	Aya Ushio, Rieko Arakaki, Kunihiro Ohtsuka, Yasusei Kudo and Naozumi Ishimaru : CCL22産生唾液腺マクロファージはシェーグレン症候群の病態に関与する, シェーグレン症候群学会, Sep. 2018.
134.	Kouji Hirao, Hiromichi Yumoto, Kunihiro Otsuka, Naozumi Ishimaru and Takashi Matsuo : 歯内由来病変と混同しやすい根尖病変様のエックス線透過像を有する症例, 第18回西日本歯内療法学会会研修会(2018年度), Sep. 2018.
135.	Kunihiro Ohtsuka, Akiko Yamada, Masako Saito, Aya Ushio, Satoru Kisoda, Takaaki Tsunematsu, Yasusei Kudo, Rieko Arakaki and Naozumi Ishimaru : シェーグレン症候群疾患モデルの自己免疫病変における濾胞ヘルパーT細胞の役割, Japanese Journal of Oral Biology, Sep. 2018.
136.	Kunihiro Ohtsuka, Akiko Yamada, Masako Saito, Aya Ushio, Satoru Kisoda, Takaaki Tsunematsu, Yasusei Kudo, Rieko Arakaki and Naozumi Ishimaru : Asc/2を介した濾胞ヘルパーT細胞分化異常が自己免疫疾患の病態形成に関与する．, 日本臨床口腔病理学会, Aug. 2018.
137.	Kunihiro Ohtsuka, Akiko Yamada, Masako Saito, Aya Ushio, Satoru Kisoda, Takaaki Tsunematsu, Yasusei Kudo, Rieko Arakaki and Naozumi Ishimaru : シェーグレン症候群疾患モデルの自己免疫病変における濾胞ヘルパーT細胞の役割, 分子病理学研究会, Jul. 2018.
138.	Naozumi Ishimaru : シェーグレン症候群における自己反応性獲得機序の解明, Proceedings of the Japanese Society of Pathology, Vol.107, Jun. 2018.
139.	Rieko Arakaki, Aya Ushio, Kunihiro Ohtsuka, Yasusei Kudo and Naozumi Ishimaru : 全身吸入暴露による多層化カーボンナノチューブの肺胞マクロファージへの影響, Proceedings of the Japanese Society of Pathology, Vol.107, Jun. 2018.
140.	Shinichiroh Nakayama, Rieko Arakaki, Aya Ushio, Kunihiro Ohtsuka, Takaaki Tsunematsu, Yasusei Kudo and Naozumi Ishimaru : シェーグレン症候群モデルマウス唾液腺におけるIL-33の発現とその役割, Proceedings of the Japanese Society of Pathology, Vol.107, Jun. 2018.
141.	Saki Saijoh, Kunihiro Ohtsuka, Takaaki Tsunematsu, Kunihiro Ohtsuka, Aya Ushio, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : Emi1の過剰発現による人工口腔癌幹細胞の作成, Proceedings of the Japanese Society of Pathology, Vol.107, Jun. 2018.
142.	Yukino Numata, Kunihiro Ohtsuka, Akiko Yamada, Aya Ushio, Takaaki Tsunematsu, Yasusei Kudo, Rieko Arakaki and Naozumi Ishimaru : シェーグレン症候群疾患モデルにおけるNotchシグナルの役割, Proceedings of the Japanese Society of Pathology, Vol.107, Jun. 2018.
143.	Kunihiro Ohtsuka, Akiko Yamada, Masako Saito, Aya Ushio, Takaaki Tsunematsu, Yasusei Kudo, Rieko Arakaki and Naozumi Ishimaru : シェーグレン症候群疾患モデルの自己免疫病変における濾胞ヘルパーT細胞の役割, Proceedings of the Japanese Society of Pathology, Vol.107, Jun. 2018.
144.	Aya Ushio, Rieko Arakaki, Akiko Yamada, Kunihiro Ohtsuka, Yasusei Kudo and Naozumi Ishimaru : CCL22-producing resident macrophages enhancesnautoimmune lesions in a mouse model of Sjogren's syndorome., Proceedings of the Japanese Society for Immunology, Vol.46, 119, Dec. 2017.
145.	Kunihiro Ohtsuka, Akiko Yamada, Aya Ushio, Mie Kurosawa, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : Analysis of follicular helper T cells in a mouse model for Sjogren's syndorome., Proceedings of the Japanese Society for Immunology, Vol.46, 81, Dec. 2017.
146.	Takashi Izawa, Rieko Arakaki, Eiji Tanaka and Naozumi Ishimaru : Crosstalk between cytokine RANKL and AhR signaling in osteoclasts controls bone homeostasis (selected for oral presentation by English at Workshop "Cytokines and chemokines-2" and poster session), Proceedings of the Japanese Society for Immunology, Vol.46, 36, Dec. 2017. (Keyword) osteoclast / RANKL / AhR
147.	Izumi Ohigashi, Naozumi Ishimaru, Katakai Tomoya and Yousuke Takahama : Essential role of CCL21 in establishment of central tolerance in T cells, 第40回日本分子生物学会年会, Dec. 2017.
148.	Takashi Izawa, Rieko Arakaki, Eiji Tanaka and Naozumi Ishimaru : The nuclear receptor AhR controls bone homeostasis by regulating osteoclast differentiation via the RANK/c-Fos signaling axis, ConBio2017 (Consortium of Biological Sciences 2017), 402, Dec. 2017. (Keyword) osteoclast / RANKL / aryl hydrocarbon receptor / c-Fos
149.	S Afroz, Iwasa Takuma, Masamitsu Ohshima, Rieko Arakaki, Miho Inoue, Naozumi Ishimaru and Yoshizo Matsuka : Cytokine released by satellite glial cells and pain transmission in sensory ganglions, Japan Association for Dental Research, Nov. 2017.
150.	Hiroki Iga, Daisuke Hinode, Yasusei Kudo, Naozumi Ishimaru and Yasuhiko Shirayama : 国際教育連携を活用した新しい歯科衛生士教育の試みと今後の展開, 第65回NPO法人日本口腔科学会中国・四国地方部会, Nov. 2017. (Keyword) 口腔保健 / 歯科衛生士
151.	Natsumi Takamaru, Hirokazu Nagai, Kazuya Akita, Yasusei Kudo, Naozumi Ishimaru and Youji Miyamoto : 翼突下顎隙に生じた紡錐細胞脂肪腫の1例, 第62回日本口腔外科学会学術大会, Oct. 2017.
152.	Kunihiro Ohtsuka, Akiko Yamada, Yasusei Kudo, Rieko Arakaki and Naozumi Ishimaru : シェーグレン症候群疾患モデルにおける胚中心反応の解析, 第26回日本シェーグレン症候群学会学術集会, Vol.26, Sep. 2017.
153.	Kunihiro Ohtsuka, Akiko Yamada, Masako Saito, Aya Ushio, Satoko Kujiraoka, Mie Kurosawa, Takaaki Tsunematsu, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : シェーグレン症候群疾患モデルにおける胚中心反応の解析, 第28回日本臨床口腔病理学会, Vol.28, Aug. 2017.
154.	Takashi Izawa, Eiji Tanaka and Naozumi Ishimaru : The nuclear receptor AhR controls bone homeostasis by regulating osteoclast differentiation via the RANK/c-Fos signaling axis, The 35th Annual Meeting of the Japanese Society for Bone and Mineral Research (oral talk), Jul. 2017.
155.	Kunihiro Ohtsuka, Yasusei Kudo and Naozumi Ishimaru : シェーグレン症候群疾患モデルにおける胚中心反応の解析, 第36回分子病理学研究会, Vol.36, Jul. 2017.
156.	Aya Ushio, Rieko Arakaki, Akiko Yamada, Kunihiro Ohtsuka, Mie Kurosawa, Yasusei Kudo and Naozumi Ishimaru : シェーグレン症候群モデルマウスの唾液腺マクロファージと病態への関与, 第16回四国免疫フォーラム, Jun. 2017.
157.	宮本由貴, Yukihiro Momota, Kohichi Kani, Fumihiro Matsumoto, Keiko Aota, Hideyuki Takano, 高瀬奈緒, Tomoko Yamanoi, Shinji Ono, 牛尾綾, Naozumi Ishimaru and Masayuki Azuma : 上顎に発生した石灰化を伴わない石灰化上皮性歯原性腫瘍の1例, 第46回日本口腔外科学会中国四国支部学術集会, May 2017.
158.	横田美保, Keiko Kudoh, Tetsuya Tamatani, 鎌田久美子, Naoyuki Fukuda, Natsumi Takamaru, Yoshiko Yamamura, Takayuki Nakagawa, Go Ohe, Takaharu Kudoh, Akira Takahashi, Kenji Fujisawa, 鯨岡聡子, Yasusei Kudo, Naozumi Ishimaru and Youji Miyamoto : 当科における歯原性角化嚢胞の臨床的検討, 第46回日本口腔外科学会中国四国学術集会, May 2017.
159.	Rieko Arakaki, Kohichi Yamada, Masako Saito, Kunihiro Ohtsuka, Akiko Yamada, Takaaki Tsunematsu, Yasusei Kudo, 菅野純 and Naozumi Ishimaru : Chronic influence of Multi-walled carbon nanotubes (MWCNT) on immune system, 第106回日本病理学会総会, Vol.106, Apr. 2017.
160.	Takaaki Tsunematsu, Yasusei Kudo, Akiko Yamada, Rieko Arakaki, Hirohisa Ogawa, Koichi Tsuneyama and Naozumi Ishimaru : 胎児性癌細胞におけるユビキチンプロテアソーム経路による未分化性維持機構, 第106回日本病理学会総会, Vol.106, Apr. 2017.
161.	Aya Ushio, Rieko Arakaki, Akiko Yamada, Kunihiro Ohtsuka, Satoko Kujiraoka, Takaaki Tsunematsu, Yasusei Kudo and Naozumi Ishimaru : シェーグレン症候群の唾液腺におけるマクロファージサブセットと病態への関与, 第106回日本病理学会総会, Vol.106, Apr. 2017.
162.	Satoko Kujiraoka, Yasusei Kudo, Takaaki Tsunematsu, Aya Ushio, Kunihiro Ohtsuka, Akiko Yamada, Rieko Arakaki and Naozumi Ishimaru : 歯原性明細胞癌細胞株の樹立とその性状解析, 第106回日本病理学会総会, Vol.106, Apr. 2017.
163.	Masaaki Umeda, Takaaki Tsunematsu, Masako Saito, Akiko Yamada, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : 口腔癌におけるPeriostinスプライシングバリアントの新たな役割, 第106回日本病理学会総会, Vol.106, Apr. 2017.
164.	Kunihiro Ohtsuka, Akiko Yamada, Masako Saito, Aya Ushio, Mie Kurosawa, Satoko Kujiraoka, Takaaki Tsunematsu, Yasusei Kudo, Rieko Arakaki and Naozumi Ishimaru : シェーグレン症候群モデルマウスにおける濾胞ヘルパーT細胞の解析, 第106回日本病理学会総会, Vol.106, Apr. 2017.
165.	Keiko Aota, 山ノ井朋子, Kohichi Kani, Naozumi Ishimaru and Masayuki Azuma : シェーグレン症候群におけるCXCR3+マクロファージの動態, 第71回日本口腔科学会学術集会, Apr. 2017.
166.	Takaaki Tsunematsu, Yasusei Kudo, Akiko Yamada, Rieko Arakaki, Hirohisa Ogawa, Koichi Tsuneyama and Naozumi Ishimaru : 胎児性癌細胞におけるユビキチンプロテアソーム経路による未分化性維持機構, Proceedings of the Japanese Society of Pathology, Vol.106, No.1, 356, Mar. 2017.
167.	Rieko Arakaki, Kohichi Yamada, Aya Ushio, Mie Kurosawa, Kunihiro Ohtsuka, Masako Saito, Takaaki Tsunematsu, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : Immunological and toxicological effect of multi-wall carbon nanotubes by whole body inhalation exposure in B6 mice, 第45回日本免疫学会学術集会, Vol.45, Dec. 2016.
168.	Akiko Yamada, Rieko Arakaki, Aya Ushio, Takaaki Tsunematsu, Yasusei Kudo and Naozumi Ishimaru : 1)Impaired Expansion of Regulatory T cells in a Murine model of Neonatal Thymectomy-induced Sjogrens Syndrome, 第45回日本免疫学会学術集会, Vol.45, Dec. 2016.
169.	Kunihiro Ohtsuka, Masako Saito, Mie Kurosawa, Aya Ushio, Akiko Yamada, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : Analysis of follicular helper T cells in a mouse model for Sjogren's syndrome., 第45回日本免疫学会学術集会, Vol.45, Dec. 2016.
170.	Aya Ushio, Rieko Arakaki, Masako Saito, Akiko Yamada, Kunihiro Ohtsuka, Mie Kurosawa, Satoko Kujiraoka, Yasusei Kudo and Naozumi Ishimaru : Analysis of macrophages in the pathogenesis of a murine model for Sjogren's syndrome., 第45回日本免疫学会学術集会, Vol.45, Dec. 2016.
171.	Keiko Aota, Tomoko Yamanoi, Kohichi Kani, Naozumi Ishimaru and Masayuki Azuma : ヒト唾液腺細胞株における CXCL10 の発現機能解析, 第53回日本口腔組織培養学会学術大会, Nov. 2016.
172.	Masahiro Hiasa, Ryota Amachi, Hirofumi Tenshin, Shinya Horiuchi, Masahiro Abe, Naozumi Ishimaru and Eiji Tanaka : RelBは古典的NF-κB経路の活性化を阻害し骨癒合不全と偽関節形成を予防する, 日本矯正歯科学会大会プログラム・抄録集., 192., Nov. 2016.
173.	Kunihiro Ohtsuka, Aya Ushio, 宮本由貴, Satoko Kujiraoka, Akiko Yamada, Keiko Aota, Yasusei Kudo, Masayuki Azuma and Naozumi Ishimaru : 1, 第64回日本口腔科学会中国四国地方部会, Vol.64, Oct. 2016.
174.	高瀬奈緒, Yukihiro Momota, Kohichi Kani, 宮本由貴, 山ノ井朋子, Shinji Ono, Hideyuki Takano, Keiko Aota, Fumihiro Matsumoto, 牛尾綾, Naozumi Ishimaru and Masayuki Azuma : 上唇粘膜下に生じた血管筋腫の1例, 第64回日本口腔科学会中四国地方部会, Oct. 2016.
175.	横田美保, Kenji Fujisawa, Yoshiko Yamamura, Tetsuya Tamatani, Natsumi Takamaru, Keiko Kudoh, Go Ohe, Hirokazu Nagai, 鯨岡聡子, Naozumi Ishimaru and Youji Miyamoto : 骨破壊を伴った顎放線菌症の2例, 第64回NPO法人日本口腔科学会中国・四国地方部会, Oct. 2016.
176.	Aya Ushio, Rieko Arakaki, Kunihiro Ohtsuka, Masako Saito, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : シェーグレン症候群の病態形成におけるマクロファージの役割, 日本シェーグレン症候群学会, Vol.25, Sep. 2016.
177.	Kunihiro Ohtsuka, Masako Saito, Aya Ushio, Akiko Yamada, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : シェーグレン症候群モデルにおける濾胞ヘルパーT細胞の機能解析, 日本シェーグレン症候群学会, Vol.25, Sep. 2016.
178.	Aya Ushio, Yasusei Kudo, Satoko Kujiraoka, Kunihiro Ohtsuka, Takaaki Tsunematsu, Akiko Yamada and Naozumi Ishimaru : 上顎骨腫瘍, 日本臨床口腔病理学会総会・学術集会, Vol.27, Aug. 2016.
179.	Satoko Kujiraoka, Yasusei Kudo, Takaaki Tsunematsu, Aya Ushio, Kunihiro Ohtsuka, Akiko Yamada and Naozumi Ishimaru : 小児に発生した歯原性下顎骨腫瘍の1例, 日本臨床口腔病理学会総会・学術集会, Vol.27, Aug. 2016.
180.	Masaaki Umeda, Takaaki Tsunematsu, Masako Saito, Akiko Yamada, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : 口腔扁平上皮癌におけるPeriostinスプライシングバリアントの新たな役割, 第27回日本臨床口腔病理学会総会・学術大会, Aug. 2016.
181.	高瀬奈緒, Keiko Aota, 宮本由貴, 山ノ井朋子, Shinji Ono, Hideyuki Takano, Kohichi Kani, Yukihiro Momota, Naozumi Ishimaru and Masayuki Azuma : 口蓋に生じた筋上皮腫の1例, 第45回日本口腔外科学会中四国支部学術集会, May 2016.
182.	Rieko Arakaki, Takaaki Tsunematsu, Akiko Yamada, Masako Saito, Yasusei Kudo and Naozumi Ishimaru : 全身吸入暴露による多層化カーボンナノチューブの免疫システムへの影響, 第105回日本病理学会総会, Vol.105, No.1, May 2016.
183.	Aya Ushio, Masako Saito, Akiko Yamada, Kunihiro Ohtsuka, Mie Kurosawa, Satoko Kujiraoka, Yasusei Kudo and Naozumi Ishimaru : シェーグレン症候群モデルマウスの病態形成におけるマクロファージの役割, 第105回日本病理学会総会, Vol.105, No.1, May 2016.
184.	Satoko Kujiraoka, Yasusei Kudo, Takaaki Tsunematsu, Tomoyuki Kondoh, Aya Ushio, Kunihiro Ohtsuka, Akiko Yamada, Rieko Arakaki and Naozumi Ishimaru : 顎骨中心性明細胞性腫瘍からの細胞株の樹立とその性状, 第105回日本病理学会総会, Vol.105, No.1, May 2016.
185.	山ノ井朋子, Keiko Aota, Hideyuki Takano, Kohichi Kani, Fumihiro Matsumoto, Yukihiro Momota, 高瀬奈緒, 宮本由貴, Naozumi Ishimaru and Masayuki Azuma : シェーグレン症候群患者におけるセファランチンの作用機序の解明, 第70回日本口腔科学会学術集会, Apr. 2016.
186.	Keiko Aota, 山ノ井朋子, Kohichi Kani, Hideyuki Takano, Yukihiro Momota, Fumihiro Matsumoto, Naozumi Ishimaru and Masayuki Azuma : Sjögren 症候群唾液腺における IP-10 の発現制御機構, 第70回日本口腔科学会学術集会, Apr. 2016.
187.	Takaaki Tsunematsu, Yasusei Kudo, Akiko Yamada, Rieko Arakaki, Hirohisa Ogawa, Hisanori Uehara, Naozumi Ishimaru and Koichi Tsuneyama : 染色体パッセンジャー複合体タンパク質Borealinのユビキチン分解の意義とその癌化への関与, Proceedings of the Japanese Society of Pathology, Vol.105, No.1, 548, Apr. 2016.
188.	Masako Saito, Rieko Arakaki, Kunihiro Ohtsuka, Kohichi Yamada, Yasusei Kudo and Naozumi Ishimaru : Biological effect of Multi-Walled Carbon Nanotubes(MWCNTs)on imune system., Proceedings of the Japanese Society for Immunology, Nov. 2015.
189.	Rieko Arakaki, Aya Ushio, Mie Kurosawa, Kunihiro Ohtsuka, Akiko Yamada, Masako Saito, Takaaki Tsunematsu, Yasusei Kudo and Naozumi Ishimaru : Analysis of function of macrophages in murine models of Sjogren's syndorome., Proceedings of the Japanese Society for Immunology, Nov. 2015.
190.	Mie Kurosawa, Akiko Yamada, Rieko Arakaki, Masako Saito, Takaaki Tsunematsu, Yasusei Kudo and Naozumi Ishimaru : Migratory activity of memory T cells in aly/aly mice., Proceedings of the Japanese Society for Immunology, Nov. 2015.
191.	Tomoyuki Kondoh, Takaaki Tsunematsu, Yasusei Kudo and Naozumi Ishimaru : 自己免疫疾患モデルにおける腫瘍増殖の亢進, 第74回日本癌学会学術総会, Oct. 2015.
192.	古川貴大, Naoko Matsui, 高橋利幸, Naozumi Ishimaru and Ryuji Kaji : 耳下腺炎後に視神経や脊髄以外に広範な白質病変を来し，抗AQP4抗体が陽性であったシェーグレン症候群の1例, 神経免疫学, Vol.20, No.1, 114, Sep. 2015.
193.	Takaaki Tsunematsu, Yasusei Kudo, Tomoyuki Kondoh, Aya Ushio, Satoko Kujiraoka, Akiko Yamada, Rieko Arakaki and Naozumi Ishimaru : 染色体パッセンジャー複合体タンパク質Borealinのユビキチン分解とその癌化への関与, 日本病理学会会誌, Vol.104, No.1, 504, May 2015.
194.	Satoko Kujiraoka, Yasusei Kudo, Takaaki Tsunematsu, Tomoyuki Kondoh, Aya Ushio, Akiko Yamada, Rieko Arakaki and Naozumi Ishimaru : 口腔癌細胞におけるペリオスチンのスプライシングバリアントの発現とその意義, 日本病理学会会誌, Vol.104, No.1, 497, Apr. 2015.
195.	Tomoyuki Kondoh, Takaaki Tsunematsu, Satoko Kujiraoka, Satoko Kujiraoka, Aya Ushio, Akiko Yamada, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : 自己免疫疾患モデルを用いた腫瘍増殖制御機構の解明, 日本病理学会会誌, Vol.104, No.1, 497, Apr. 2015.
196.	Aya Ushio, Rieko Arakaki, Tomoyuki Kondoh, Satoko Kujiraoka, Takaaki Tsunematsu, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : Analysis of macrophages in the pathogenesis of a murine for Sjogren's syndorome., 日本病理学会会誌, Vol.104, No.1, 450, Apr. 2015.
197.	Yasusei Kudo, Takaaki Tsunematsu, Satoko Kujiraoka, Tomoyuki Kondoh, Aya Ushio, Akiko Yamada, Rieko Arakaki and Naozumi Ishimaru : 顎骨中心性粘表皮癌細胞株の樹立とその性状, 日本病理学会会誌, Vol.104, No.1, 401, Apr. 2015.
198.	Rieko Arakaki, Takaaki Tsunematsu, Akiko Yamada, Yasusei Kudo, 菅野純 and Naozumi Ishimaru : 自己免疫疾患モデルマウスを利用した多層化カーボンナノチューブの免疫システムへの影響, 日本病理学会会誌, Vol.104, No.1, 380, Apr. 2015.
199.	Aya Ushio, Rieko Arakaki, Mie Kurosawa, Tomoyuki Kondoh, Satoko Kujiraoka, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : Analysis of macrophages in the pathogenesis of murine models for Sjogren's syndorome., Proceedings of the Japanese Society for Immunology, Dec. 2014.
200.	Rieko Arakaki, Aya Ushio, Kohichi Yamada, Mie Kurosawa, Satoko Kujiraoka, Tomoyuki Kondoh, 常松貴明, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : Influence of multi-wall carbon nanotubes on immune system in nomal mice and MRL/lpr mice., Proceedings of the Japanese Society for Immunology, Dec. 2014.
201.	Mie Kurosawa, Akiko Yamada, Rieko Arakaki, Tomoyuki Kondoh, 常松貴明, Yasusei Kudo, Satoko Kujiraoka, Aya Ushio and Naozumi Ishimaru : A novel role of CXCR7 in memory T cells of a murine model for Sjogren's syndorome., Proceedings of the Japanese Society for Immunology, Dec. 2014.
202.	Naozumi Ishimaru : 病気と研究∼自己免疫疾患の克服にむけて∼, 九州歯科大学, Dec. 2014.
203.	Naozumi Ishimaru : シェーグレン症候群の病態機序, 日本皮膚科四国地方会, Dec. 2014.
204.	Satoko Kujiraoka, Yasusei Kudo, 常松貴明 and Naozumi Ishimaru : 口腔癌細胞におけるペリオスチンのスプライシングバリアントの発現とその意義, 第37回日本分子生物学会, Nov. 2014.
205.	Takaharu Kudoh, Nobuyuki Kuribayashi, Keiko Kudoh, Go Ohe, Masako Fujioka-Kobayashi, Tetsuya Tamatani, Hirokazu Nagai, 近藤智之, Naozumi Ishimaru and Youji Miyamoto : 舌に発生した孤立性神経線維腫の1例, 第62回NPO法人日本口腔科学会中国・四国地方部会, Oct. 2014.
206.	Aya Ushio, Rieko Arakaki, Mie Kurosawa, Tomoyuki Kondoh, Satoko Kujiraoka, 常松貴明, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : シェーグレン症候群モデルマウスの標的臓器におけるマクロファージの役割, 日本シェーグレン症候群学会学術集会, Sep. 2014.
207.	Yosuke Shikama, Yasusei Kudo, Naozumi Ishimaru and Makoto Funaki : 飽和脂肪酸が歯周病の病態形成に関与する可能性(Possibility of involvement of saturated fatty acids in pathogenesis of periodontitis), Journal of Oral Biosciences Supplement, Vol.2014, 161, Sep. 2014.
208.	Tomoyuki Kondoh, 常松貴明, Mie Kurosawa, Satoko Kujiraoka, Aya Ushio, Akiko Yamada, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : Analysis of regulatory mechanism of tumor immunity using an animal model for autoimmunity., 第25回日本臨床口腔病理学会, Aug. 2014.
209.	Aya Ushio, Rieko Arakaki, Mie Kurosawa, Tomoyuki Kondoh, Satoko Kujiraoka, 常松貴明, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : Analysis of macrophages in the pathogenesis of Sjogren's syndrome using murine models., 第25回日本臨床口腔病理学会, Aug. 2014.
210.	Satoko Kujiraoka, Yasusei Kudo, 常松貴明, Tomoyuki Kondoh, Aya Ushio, Mie Kurosawa, Akiko Yamada, Rieko Arakaki and Naozumi Ishimaru : The role of splicing variants of periostin in oral cancer cells., 第25回日本臨床口腔病理学会, Aug. 2014.
211.	Tomoyuki Kondoh, Satoko Kujiraoka, Aya Ushio, Mie Kurosawa, 常松貴明, Akiko Yamada, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : 自己免疫疾患モデルを用いた腫瘍増殖抑制機構の解明, 免疫サマースクール2014, Jul. 2014.
212.	Tomoyuki Kondoh, Satoko Kujiraoka, Aya Ushio, Mie Kurosawa, 常松貴明, Akiko Yamada, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : 自己免疫疾患モデルを用いた腫瘍増殖制御機構の解明, 第33回分子病理学研究会, Jul. 2014.
213.	Keiko Aota, Yoshiko Yamamura, Kohichi Kani, Hideyuki Takano, Katsumi Motegi, Fumihiro Matsumoto, Naozumi Ishimaru and Masayuki Azuma : ドライマウス患者における唾液中のTNF-αとMMP-9発現に関する研究, 第68回日本口腔科学会学術集会, May 2014.
214.	Yasusei Kudo, 常松貴明, Tomoyuki Kondoh, Mie Kurosawa, Akiko Yamada, Rieko Arakaki and Naozumi Ishimaru : 癌細胞におけるペリオスチンのスプライシングバリアントの発現とEMTとの関連, 日本病理学会会誌, Vol.103, No.1, 268, Apr. 2014.
215.	Akiko Yamada, Rieko Arakaki, Mie Kurosawa, Tomoyuki Kondoh, 常松貴明, Yasusei Kudo, Yoshio Hayashi and Naozumi Ishimaru : シェーグレン症候群の発症における制御性T細胞の役割, 日本病理学会会誌, Vol.103, No.1, 268, Apr. 2014.
216.	Rieko Arakaki, Akiko Yamada, Yasusei Kudo, Yoshio Hayashi and Naozumi Ishimaru : ニッケルアレルギー発症におけるThmic Stromal Lymphopoiethinの重要性, 日本病理学会会誌, Vol.103, No.1, 268, Apr. 2014.
217.	Naozumi Ishimaru : シェーグレン症候群の発症機序の解明, 日本口腔外科学会中国四国支部集会, Apr. 2014.
218.	常松貴明, Yasusei Kudo, Tomoyuki Kondoh, Mie Kurosawa, Akiko Yamada, Rieko Arakaki and Naozumi Ishimaru : ユビキチン分解による複製前複合体形成因子CDT1の発現制御機構の解析, 日本病理学会会誌, Vol.103, No.1, 268, Apr. 2014.
219.	Tomoyuki Kondoh, Mie Kurosawa, 常松貴明, Akiko Yamada, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : 自己免疫疾患モデルを用いた腫瘍免疫制御機構の解析, 日本病理学会会誌, Vol.103, No.1, 268, Apr. 2014.
220.	Mie Kurosawa, Naozumi Ishimaru, Rieko Arakaki, Akiko Yamada, Yasusei Kudo and Tomoyuki Kondoh : Anovel role of CXCR7 in controlling autoreactive T cells of a murine model for Sjogren's syndorome., Proceedings of the Japanese Society for Immunology, Dec. 2013.
221.	Akihiko Iwasa, Mie Kurosawa, Rieko Arakaki, Akiko Yamada, Eiji Tanaka, Yasusei Kudo and Naozumi Ishimaru : Relationship between aromatase-related obesity and autoimmunity in Sjogren's syndorome., Proceedings of the Japanese Society for Immunology, Dec. 2013.
222.	Rieko Arakaki, Hiroshi Eguchi, Akiko Yamada, Yasusei Kudo, Yoshinori Mitamura, Yoshio Hayashi and Naozumi Ishimaru : Eye drop administration of rebamipide is effective to a dry eye symptom in a model mice of Sjogren's syndorome., Proceedings of the Japanese Society for Immunology, Dec. 2013.
223.	Yasusei Kudo, 常松貴明 and Naozumi Ishimaru : Aurora-A controls pre-replicative complex formation and DNA replication by promoting the stabilization of geminin and CDT1 in mitosis., 第36回日本分子生物学会年会, Dec. 2013.
224.	Akihiko Iwasa, Naozumi Ishimaru, Takashi Izawa, 徳永律子, Yasusei Kudo and Eiji Tanaka : アロマターゼ遺伝子欠損マウスにおけるシェーグレン症候群様病変と肥満との関連, 第72回日本矯正歯科学会大会プログラム・抄録集, Oct. 2013.
225.	Tomoyuki Kondoh, Akiko Yamada, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : 自己免疫疾患モデルを用いた腫瘍免疫システムの解析, Japanese Journal of Oral Biology, Sep. 2013.
226.	Naozumi Ishimaru : シェーグレン症候群の病理診断の新機軸, 第22回日本シェーグレン症候群学会学術集会, Sep. 2013.
227.	Tomoyuki Kondoh, Yasusei Kudo and Naozumi Ishimaru : 自己免疫疾患モデルを用いた腫瘍免疫システムの解析, 第32回分子病理学研究会, Jul. 2013.
228.	Yasusei Kudo, Takaaki Tsunematsu and Naozumi Ishimaru : Aurora-A controls pre-replicative complex formation and DNA replication by promoting the stabilization of geminin and Cdt1 in mitosis, 第35回Naito Conference, Jul. 2013.
229.	Akihiko Iwasa, Rieko Arakaki, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : アロマターぜ遺伝子欠損マウスにおけるシェーグレン症候群様病変と肥満との関連, 四国免疫ファオーラム, Jun. 2013.
230.	Akiko Yamada, Rieko Arakaki, Mie Kurosawa, Tomoyuki Kondoh, Yasusei Kudo and Naozumi Ishimaru : シェーグレン症候群における制御性T細胞の機能解析, 第102回日本病理学会, Jun. 2013.
231.	Rieko Arakaki, Akiko Yamada, Yasusei Kudo, Hiroshi Eguchi, Yoshinori Mitamura, Yoshio Hayashi and Naozumi Ishimaru : シェーグレン症候群モデルを用いたレバミピド点眼薬によるドライアイの改善効果とその作用機序, 第102回日本病理学会, Jun. 2013.
232.	Tomoyuki Kondoh, Yasusei Kudo, Akiko Yamada and Naozumi Ishimaru : 自己免疫疾患モデルを用いた腫瘍免疫システムの解析, 第102回日本病理学会, Jun. 2013.
233.	Akihiko Iwasa, Tomoyuki Kondoh, Mie Kurosawa, Rieko Arakaki, Akiko Yamada, Eiji Tanaka, Yasusei Kudo and Naozumi Ishimaru : アロマターゼ遺伝子欠損マウスにおける肥満とシェーグレン症候群様病変との関連, 第102回日本病理学会, Jun. 2013.
234.	Keiko Aota, Yoshiko Yamamura, Kohichi Kani, Hideyuki Takano, Yukihiro Momota, Fumihiro Matsumoto, Naozumi Ishimaru and Masayuki Azuma : シェーグレン症候群に対する新規治療戦略―唾液腺腺房構造の破壊を阻止する-, 第67回日本口腔科学会学術集会, May 2013.
235.	Tomoyuki Kondoh, Yasusei Kudo and Naozumi Ishimaru : 自己免疫疾患モデルを用いた腫瘍免疫システムの解析, Journal of The Japanese Stomatological Society, Vol.67, 200, May 2013.
236.	Hiroyuki Mizuguchi, 服部将史, 馬場祐子, 張倩, 小林誠, Naozumi Ishimaru, Yoshiaki Kitamura, Noriaki Takeda and Hiroyuki Fukui : タンパクキナーゼCδシグナル抑制化合物ケルセチンのストレプトゾトシン誘発β細胞破壊に対する効果, 日本薬学会第133回年会, Mar. 2013.
237.	服部将史, Hiroyuki Mizuguchi, 馬場祐子, 小野将平, 張倩, 小林誠, Naozumi Ishimaru, Yoshiaki Kitamura, Noriaki Takeda and Hiroyuki Fukui : Effect of quercetin on streptozotocin-induced diabetic mice., 第86回日本薬理学会年会, Mar. 2013.
238.	Nobuyuki Kuribayashi, Hirokazu Nagai, Daisuke Uchida, 木内誠, Tetsuya Tamatani, Kenji Fujisawa, Naozumi Ishimaru and Youji Miyamoto : 頬粘膜に生じた明細胞癌NOSの1例, 第31回日本口腔腫瘍学会総会・学術大会, Jan. 2013.
239.	Yosuke Shikama, Naozumi Ishimaru, Yukiko Bandou, Nanako Aki and Makoto Funaki : Palmitate induces IL-6 production and α-fodrin degradation in salivary gland epithelial cells, Journal of the The Japan Diabetes Society, Vol.56, No.Suppl.1, S-186, 2013. (Keyword) Carrier Proteins Interleukin 6 ミクロフィラメント蛋白質 Palmitic Acid Sjoegren症候群自己免疫疾患上皮細胞唾液腺 *Fodrin
240.	Naozumi Ishimaru : Molecular Pathogenesis of Sjogrens Syndrome, JADR, Dec. 2012.
241.	Rieko Arakaki, Hiroshi Eguchi, Akiko Yamada, Yasusei Kudo, Yoshinori Mitamura, Yoshio Hayashi and Naozumi Ishimaru : An Effective Therapy of Ocular Lesions in a Murine Model for Sjogren's Syndorome by Eye Drop Administration of Rebamipide., Proceedings of the Japanese Society for Immunology, Dec. 2012.
242.	Mie Kurosawa, Akiko Yamada, Rieko Arakaki, Tomoyuki Kondo, Yasusei Kudo and Naozumi Ishimaru : Analysis of infiltrating immune cells in the target tissues of murine models for Sjogren's syndorome., Proceedings of the Japanese Society for Immunology, Dec. 2012.
243.	Akiko Yamada, Rieko Arakaki, Mie Kurosawa, Tomoyuki Kondo, Yasusei Kudo, Yoshio Hayashi and Naozumi Ishimaru : Functional defect of Foxp3+Treg cells in Sjogren's syndrome., Proceedings of the Japanese Society for Immunology, Dec. 2012.
244.	Akihiko Iwasa, Rieko Arakaki, Akiko Yamada, Eiji Tanaka, Yasusei Kudo and Naozumi Ishimaru : The dysfunction of the aromatase worsens the pathogenesis of Sjogren's syndrome., Proceedings of the Japanese Society for Immunology, Dec. 2012.
245.	Daisuke Tsuji, 難波建多郎, Naozumi Ishimaru, 櫻庭均 and Kouji Itou : Tay-Sachs病患者由来iPS細胞の樹立と分化神経系細胞に対する酵素補充効果の検討, 第54回日本先天代謝異常学会総会/第11回アジア先天代謝異常症シンポジウム, Nov. 2012.
246.	Hirokazu Nagai, Kenji Fujisawa, Natsumi Takamaru, Daisuke Uchida, Tetsuya Tamatani, Go Ohe, Naozumi Ishimaru and Youji Miyamoto : 頬部に生じた粘液種の1例, 第57回公益社団法人日本口腔外科学会, Oct. 2012.
247.	近藤智之, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : 口蓋に生じた悪性リンパ腫の2症例, 第60回日本口腔科学会中国・四国地方部会, Oct. 2012.
248.	近藤智之, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : 口蓋に生じた悪性リンパ腫の2症例, 第23回日本臨床口腔病理学会, Sep. 2012.
249.	Yasusei Kudo, 常松貴明, 近藤智之, Naozumi Ishimaru and Takashi Takata : Chromosome passenger complex protein,Borealin is regulated by APC/C-Cdh1 ubiquitin ligase complex, Proceedings of the Japanese Cancer Association, Sep. 2012.
250.	Akiko Yamada, Rieko Arakaki, 黒澤愛実, 近藤智之, Yasusei Kudo and Naozumi Ishimaru : シェーグレン症候群における制御性T細胞の役割, 第21回日本シェーグレン症候群学会, Sep. 2012.
251.	Rieko Arakaki, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : エストロゲン欠乏によって増悪されるシェーグレン症候群病態へのTh17細胞の関与, Japanese Journal of Oral Biology, Vol.54, 145-145, Sep. 2012.
252.	服部将史, Hiroyuki Mizuguchi, 馬場祐子, 張倩, 小林誠, 小野将平, Naozumi Ishimaru and Hiroyuki Fukui : プロテインキナーゼC(PKC)-δシグナル抑制効果をもつ新規抗糖尿病薬開発及び糖尿病発症メカニズムの解明, 第11回次世代を担う若手ファーマ・バイオフォーラム2012, Sep. 2012.
253.	Naozumi Ishimaru : シェーグレン症候群の臨床応用研究, 第23回日本臨床口腔病理学会, Aug. 2012.
254.	Naozumi Ishimaru : シェーグレン症候群の発症機序と臨床応用研究, 第23回日本臨床口腔病理学会, Aug. 2012.
255.	Akihiko Iwasa, Rieko Arakaki, Akiko Yamada, Yasusei Kudo and Naozumi Ishimaru : A critical role of aromatase in the pathogenesis of Sjogren's syndrome, 第31回分子病理学研究会, Jul. 2012.
256.	Masahiro Hiasa, Masahiro Abe, Rieko Arakaki, Akiko Yamada, Kenzo Asaoka, Toshio Matsumoto, Yoshio Hayashi and Naozumi Ishimaru : RelB antagonizes the classical NF-κB pathway and its suppression of osteoblastogenesis, 第30回日本骨代謝学会, Jul. 2012.
257.	Keiko Aota, Katsumi Motegi, Yukihiro Momota, Naozumi Ishimaru and Masayuki Azuma : シェーグレン症候群患者の唾液腺腺房構造破壊阻止―セファランチンの有効性に関する臨床病理学的研究―, 第66回日本口腔科学会学術総会, May 2012.
258.	Akiko Yamada, Rieko Arakaki, Yoshio Hayashi and Naozumi Ishimaru : シェーグレン症候群における制御性T細胞の役割, 第101回日本病理学会, Apr. 2012.
259.	Ritsuko 徳永律子 Oura, Rieko Arakaki, Akiko Yamada, Yoshio Hayashi and Naozumi Ishimaru : Fas分子を介したマクロファージによる末梢T細胞の維持機構, 第101回日本病理学会, Apr. 2012.
260.	Naozumi Ishimaru, Akiko Yamada, Rieko Arakaki and Yoshio Hayashi : 自己免疫疾患におけるCCR7を介した制御性T細胞のパトローリング機能, 第101回日本病理学会, Apr. 2012.
261.	Rieko Arakaki, Akiko Yamada, Yoshio Hayashi, Hiroshi Eguchi, 三田村さやか, 堀田芙美香, Yoshinori Mitamura and Naozumi Ishimaru : シェーグレン症候群モデルマウスを利用したレバミピド点眼投与による病態抑制機序の解明, 第101回日本病理学会, Apr. 2012.
262.	Naozumi Ishimaru : ライフサイエンスにおける口腔病理学の新展開, 四国歯学会教授就任講演, Mar. 2012.
263.	Naozumi Ishimaru : Analysis of Organ-Specific Autoimmune Disease, New Horizons in the Immune System Symposium, Feb. 2012.
264.	Naozumi Ishimaru : 口腔乾燥症の病態機序と治療戦略, 第7回次世代医療システム産業化フォーラム, Jan. 2012.
265.	Kazuma Matsumoto, Rieko Arakaki, Akiko Yamada, Masahiro Hiasa, Ritsuko 徳永律子 Oura, 岩浅亮彦, Eiji Tanaka, Yoshio Hayashi and Naozumi Ishimaru : Hyperfunctions of osteoclasts in pathogenesis of rheumatoid arthritis in MRL/lpr mice., 第40回日本免疫学会学術集会, Nov. 2011.
266.	Masahiro Hiasa, Rieko Arakaki, Akiko Yamada, Ritsuko 徳永律子 Oura, Masahiro Abe, Toshio Matsumoto, Yoshio Hayashi, Naozumi Ishimaru and Kenzo Asaoka : A novel role of NF-B relB in bone remodeling., 第40回日本免疫学会学術集会, Nov. 2011.
267.	Ritsuko 徳永律子 Oura, Rieko Arakaki, Masahiro Hiasa, Akiko Yamada, Eiji Tanaka, Yoshio Hayashi and Naozumi Ishimaru : In vivo T cell apoptosis via interaction with CD11b+ macrophages in Fas-deficient host., Proceedings of the Japanese Society for Immunology, Vol.40, 111, Nov. 2011.
268.	Akihiko Iwasa, Rieko Arakaki, Akiko Yamada, Eiji Tanaka, Yoshio Hayashi and Naozumi Ishimaru : A critical role of aromatase in the pathogenesis of Sjogren's syndrome., Proceedings of the Japanese Society for Immunology, Vol.40, 127, Nov. 2011.
269.	Rieko Arakaki, Akiko Yamada, Yoshio Hayashi and Naozumi Ishimaru : The role of Th17 cell on the development of Sjogren's syndrome in estrogen deficient NOD mice., Proceedings of the Japanese Society for Immunology, Vol.40, 128, Nov. 2011.
270.	Nur Meinar Ashrin, Megumi Watanabe, Rieko Arakaki, Akiko Yamada, Tetsuo Ichikawa, Yoshio Hayashi and Naozumi Ishimaru : Analysis of Immune Responess to Metal using Murine Nickel Allergy Model., Proceedings of the Japanese Society for Immunology, Vol.40, 102, Nov. 2011.
271.	Naozumi Ishimaru : 口腔免疫疾患の分子メカニズムと治療戦略, 日本口腔科学会中四国支部会, Nov. 2011.
272.	Naozumi Ishimaru : 口腔免疫疾患の分子メカニズムと治療戦略, 第59回NPO法人日本口腔科学会中国・四国地方部会, Nov. 2011.
273.	Naozumi Ishimaru : 免疫学から見た病理学, 日本臨床衛生検査所中四国支部会, Nov. 2011.
274.	Naozumi Ishimaru : 口腔乾燥症の病態機序と治療戦略, 徳島大学大学院ヘルスバイオサイエンス研究部公開市民講座, Nov. 2011.
275.	Naozumi Ishimaru : イメージング技術を用いた臓器特異的自己免疫疾患の病態解明, 第3回革新的特色研究シンポジウム, Nov. 2011.
276.	近藤真代, Hiroshi Kawano, Souji Kakiuchi, Jun Kishi, Masaki Hanibuchi, Masahiko Azuma, 近藤絵里, Masakazu Goda, Naozumi Ishimaru and Yasuhiko Nishioka : IgG4関連下垂体炎の1例, 第105回日本内科学会四国地方会, Nov. 2011.
277.	Natsumi Takamaru, Hirokazu Nagai, Go Ohe, Daisuke Uchida, Tetsuya Tamatani, Naozumi Ishimaru and Youji Miyamoto : 下顎骨に発生した歯原性粘液腫の1例, 第 56回日本口腔外科学会総会・学術大会, Oct. 2011.
278.	Kazuma Matsumoto, Naozumi Ishimaru, Takashi Izawa, Masahiro Hiasa, Ritsuko 徳永律子 Oura, Akihiko Iwasa, Yoshio Hayashi and Eiji Tanaka : 関節リウマチモデルマウスにおける破骨細胞の機能亢進, 日本矯正歯科学会大会プログラム・抄録集, 218, Oct. 2011. (Keyword) 関節リウマチ(実験的); 疾患モデル(動物); 破骨細胞 / マウス; 動物; 歯学
279.	Naozumi Ishimaru : 臓器特異的自己免疫疾患の病態解明に向けた多角的研究, 第53回歯科基礎医学会学術大会, Oct. 2011.
280.	Kazuma Matsumoto, Naozumi Ishimaru, Takashi Izawa, Masahiro Hiasa, Eiji Tanaka and Yoshio Hayashi : 関節リウマチモデルマウスにおける破骨細胞の機能解析, The Annual Meeting of the Japanese Society for Bone and Mineral Research Program & Abstracts, 256, Jul. 2011.
281.	Naozumi Ishimaru : 口腔乾燥症の病態機序と治療戦略, 第9回徳島大学研究者との集い, Jul. 2011.
282.	Kazuma Matsumoto, Naozumi Ishimaru, Takashi Izawa, Ritsuko 徳永律子 Oura, Akihiko Iwasa, Yoshio Hayashi and Eiji Tanaka : Analysis for mechanism of T cell activation via osteoclast in rheumatoid arthritis, Journal of the Japanese Society for the Temporomandibular Joint, Vol.23, 102, Jul. 2011.
283.	Naozumi Ishimaru : 自己免疫疾患発症機序の解明∼疾患モデルから臨床応用に向けて∼, 第30回分子病理学研究会瀬戸内シンポジウム, Apr. 2011.
284.	Kazuma Matsumoto, Naozumi Ishimaru, Rieko Arakaki, Akiko Yamada, Eiji Tanaka and Yoshio Hayashi : 関節リウマチ病態における破骨細胞を介したT細胞活性化機構の解析, 第100回日本病理学会学術集会, Vol.100, No.1, 60, Apr. 2011.
285.	Rieko Arakaki, Naozumi Ishimaru, Akiko Yamada and Yoshio Hayashi : エストロゲン欠乏によって誘導されるシェーグレン症候群病態増強へのTh17細胞の関与, 第100回日本病理学会学術集会, Vol.100, No.1, 63, Apr. 2011.
286.	Naozumi Ishimaru, Akiko Yamada, Rieko Arakaki and Yoshio Hayashi : 自己免疫疾患の病態におけるメモリーCD8陽性T細胞の役割, 第100回日本病理学会学術集会, Vol.100, No.1, 59, Apr. 2011.
287.	Kazuma Matsumoto, Naozumi Ishimaru, Takashi Izawa, Masahiro Hiasa, Eiji Tanaka and Yoshio Hayashi : 関節リウマチモデルマウスにおける破骨細胞の機能解析, The Annual Meeting of the Japanese Society for Bone and Mineral Research Program & Abstracts, 256, 2011. (Keyword) 関節リウマチ(実験的); 疾患モデル(動物); 破骨細胞 / マウス; 動物; 歯学
288.	Naozumi Ishimaru, 本間尚子, 吉村憲子, 原田信広 and Yoshio Hayashi : 自己免疫疾患におけるアロマターゼの役割, 第18回ステロイドホルモン学会学術集会, Nov. 2010.
289.	Kazuma Matsumoto, Naozumi Ishimaru, Takashi Izawa, Yoshio Hayashi and Eiji Tanaka : Analysis of osteoclast activation in the pathogenesis of rheumatoid arthritis, 58th JADR, Nov. 2010.
290.	Hiroyuki Mizuguchi, 玉田美咲, Naozumi Ishimaru, Yoshiaki Kitamura, Yoshio Hayashi, Noriaki Takeda and Hiroyuki Fukui : 鼻過敏症ラット鼻粘膜におけるヒスタミンシグナルとサイトカインシグナルのクロストーク, 日本薬理学会第118回近畿部会, Nov. 2010.
291.	Ritsuko 徳永律子 Oura, Naozumi Ishimaru, Masahiro Hiasa, Kazuma Matsumoto, Yoshio Hayashi and Eiji Tanaka : Fasを介した末梢T細胞維持機構の破綻による関節リウマチ発症機序の解明, 第69回日本矯正歯科学会, Sep. 2010.
292.	Ritsuko 徳永律子 Oura, Naozumi Ishimaru, Akiko Yamada, Rieko Arakaki, Eiji Tanaka and Yoshio Hayashi : Fas分子を介したマクロファージによる末梢T細胞の維持機構, 日本病理学会, Vol.99, No.1, 374, Apr. 2010.
293.	Kazuma Matsumoto, Naozumi Ishimaru, Rieko Arakaki, Akiko Yamada, Ritsuko 徳永律子 Oura, Eiji Tanaka and Yoshio Hayashi : マウス関節炎モデル樹状細胞のRANKL/Fasシグナルを介した免疫抑制効果, 日本病理学会, Vol.99, No.1, 220, Apr. 2010.
294.	Naozumi Ishimaru, Akiko Yamada, Rieko Arakaki and Yoshio Hayashi : シェーグレン症候群における調節性T細胞の役割, 日本病理学会会誌, Vol.99, No.1, 228, Apr. 2010.
295.	Akiko Yamada, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : Ⅰ型糖尿病モデルマウスにおけるカテプシンL特異的阻害剤を用いた治療効果の検討, 日本病理学会会誌, Vol.99, No.1, 222, Apr. 2010.
296.	Kazuma Matsumoto, Naozumi Ishimaru, Rieko Arakaki, Akiko Yamada, Ritsuko 徳永律子 Oura, Eiji Tanaka and Yoshio Hayashi : マウス関節炎モデル樹状細胞のRANKL/FASシグナルを介した免疫抑制効果, 日本病理学会会誌, Vol.99, No.1, 220, Apr. 2010.
297.	Rieko Arakaki, Naozumi Ishimaru, Akiko Yamada and Yoshio Hayashi : エストロゲン欠乏依存的に唾液腺に誘導される膵ラ氏島アミロイドポリペプチドの機能とその意義, 日本病理学会会誌, Vol.99, 307, Apr. 2010.
298.	玉田美咲, Hiroyuki Mizuguchi, Naozumi Ishimaru, Yoshiaki Kitamura, Yoshio Hayashi, Noriaki Takeda and Hiroyuki Fukui : ラット鼻粘膜におけるヒスタミンとインターロイキン -4 のクロストーク, 日本薬学会第130年会, Mar. 2010.
299.	Akiko Yamada, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : Therapeutic Analysis by Selective Inhibition of Cathepsin L for Autoimmune Diabetes in NOD Mice, 日本免疫学会総会・学術集会, Dec. 2009.
300.	Kazuma Matsumoto, Naozumi Ishimaru, Takashi Izawa, Rieko Arakaki, Ritsuko 徳永律子 Oura, Eiji Tanaka and Yoshio Hayashi : Immunoregulatory effect via RANKL and Fas signaling of dendritic cells in immurine autoimmune arthritis models, 日本免疫学会総会・学術集会, Dec. 2009.
301.	Ritsuko 徳永律子 Oura, Naozumi Ishimaru, Akiko Yamada, Rieko Arakaki, Takashi Izawa, Kazuma Matsumoto, Eiji Tanaka and Yoshio Hayashi : Immune Regulation by Macrophages through cross-talk between Fas and NF-B Signaling, 日本免疫学会総会・学術集会, Dec. 2009.
302.	Naozumi Ishimaru, Rieko Arakaki, Akiko Yamada, Yousuke Takahama and Yoshio Hayashi : In situ patrolling of regulatory T cells is essential for protecting organ-specific autoimmunity, 日本免疫学会総会・学術集会, Dec. 2009.
303.	Masayuki Kohashi, Naozumi Ishimaru, Akiko Yamada, Rieko Arakaki and Yoshio Hayashi : Neonatal exposure to low-dose 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)causes autoimmunity due to the disruption of Tcell tolerance, 2009日本免疫学会総会・学術集会記録, Vol.39, Dec. 2009.
304.	Takeo Iwata, Naozumi Ishimaru, Yoshio Hayashi, Noriko Mizusawa and Katsuhiko Yoshimoto : 脂肪組織におけるYKL-40の役割, 第51回歯科基礎医学会学術大会, Sep. 2009.
305.	Naozumi Ishimaru, Akiko Yamada, Rieko Arakaki and Yoshio Hayashi : Local Toleranceの破綻による臓器特異的自己免疫疾患の発症機序, 日本病理学会会誌, Vol.98, No.1, 249, May 2009.
306.	Rieko Arakaki, Naozumi Ishimaru, Akiko Yamada and Yoshio Hayashi : エストロゲン欠乏によって唾液腺に誘導される樹状細胞の同定とその機能, 日本病理学会会誌, Vol.98, No.1, 365, May 2009.
307.	Akiko Yamada, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : Ⅰ型糖尿病マウスにおけるカテプシンLを介した治療学的解析, 日本病理学会会誌, Vol.98, No.1, 240, May 2009.
308.	Takashi Izawa, Naozumi Ishimaru, Rieko Arakaki, Ritsuko 徳永律子 Oura, Eiji Tanaka and Yoshio Hayashi : Analysis of RANKL and Fas signaling through NF-kB in dendritic cell activation in murine autoimmune arthritis models, Proceedings of the Japanese Society for Immunology, Vol.38, 176, Dec. 2008.
309.	Rieko Arakaki, Naozumi Ishimaru, Akiko Yamada and Yoshio Hayashi : Identification and functional analysis of CD11c+B220+ dendritic cells induced by estrogen deficiency in salivary glands ., 第38回日本免疫学会総会・学術集会, Vol.38, 97, Dec. 2008.
310.	Naozumi Ishimaru, Kohashi Masayuki, Akiko Yamada, Rieko Arakaki and Yoshio Hayashi : Neonatal exposure to low-dose 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)causes autoimmunity due to the disruption of T cell tolerance, 第38回日本免疫学会総会・学術集会, Vol.38, 97, Dec. 2008.
311.	Akiko Yamada, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : Therapeutic analysis for autoimmune diabetes in NOD mice using specific inhibitor for cathepsin L, 第38回日本免疫学会総会・学術集会, Vol.38, 93, Dec. 2008.
312.	Hiroyoshi Hosokawa, Kazuhito Satomura, Keiko Kudoh, Seiko Tatehara, Reiko Tokuyama, Hideyuki Takano, Masaru Nagayama, Naozumi Ishimaru and Yoshio Hayashi : 頬粘膜に発生した血管筋腫の1例, Journal of The Japanese Stomatological Society, Vol.57, No.3, 348, Jul. 2008.
313.	Hiroyoshi Hosokawa, Kazuhito Satomura, Keiko Kudoh, Seiko Tatehara, Reiko Tokuyama, 高野栄之, Naozumi Ishimaru, Yoshio Hayashi and Masaru Nagayama : 頬粘膜に発生した血管筋腫の1例, Journal of The Japanese Stomatological Society, Vol.57, No.3, 348, Jul. 2008.
314.	Hoang Nam Tran, Takashi Sakai, Salah M. El-Sayed, Li Liu, Rika Sakai, Naozumi Ishimaru, Yoshio Hayashi, Ryuji Kaji and Kiyoshi Fukui : 新規アポトーシス制御分子ヌクリングはNF-κB の制御に関与する, 第49回日本生化学会中国四国支部例会, May 2008.
315.	Naozumi Ishimaru and Yoshio Hayashi : 自己免疫病と性差, 第97回日本病理学会総会, Vol.97, No.1, 170, May 2008.
316.	Rieko Arakaki, Naozumi Ishimaru, Akiko Yamada and Yoshio Hayashi : エストロゲン欠乏による外分泌腺上皮クラスⅡ発現の誘導メカニズム, 第97回日本病理学会総会, Vol.97, No.1, 322, May 2008.
317.	Akiko Yamada, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : Ⅰ型糖尿病モデルマウスにおけるカテプシンL阻害剤を用いた治療学的解析, 第97回日本病理学会総会, Vol.97, No.1, 266, May 2008.
318.	Naozumi Ishimaru : 自己免疫疾患におけるT細胞抑制機構, 第62回日本口腔科学会学術集会, 101, Apr. 2008.
319.	Naozumi Ishimaru : 自己免疫疾患におけるT細胞の抑制機構, 第6回口腔医学フロンティア, Feb. 2008.
320.	Takashi Sakai, HoangNam Tran, Li Liu, Xichuan Teng, Naozumi Ishimaru, Rika Sakai, Nobuya Sano, Ryuji Kaji, Yoshio Hayashi and Kiyoshi Fukui : Nucling is essential for the maintenance of Kupffer cells related to tumorgenesis in liver, The 30th Annual Meetings of the Molecular Biology Society of Japan/The 80th Annual Meeting of the Japanese Biochemical Society, Dec. 2007.
321.	Naozumi Ishimaru : 自己免疫疾患におけるNF-kBシグナルを介したT細胞の抑制機構, 日本病理学会秋期総会A演説, Dec. 2007.
322.	Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : IFN-γ-producing epithelial cells links autoimmune exocrinopathy resembling SS in RbAp48 TG mice, 第37回日本免疫学会総会・学術集会, Vol.37, 263, Nov. 2007.
323.	Rieko Arakaki, Naozumi Ishimaru, Akiko Yamada and Yoshio Hayashi : Role of estrogen deficiency for aberrant MHC class 2 expression in the exocring gland cells, 第37回日本免疫学会総会・学術集会, Vol.37, 265, Nov. 2007.
324.	Akiko Yamada, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : T cell functions with aging in NF-kB1-deficient mice, 第37回日本免疫学会総会・学術集会, Vol.37, 174, Nov. 2007.
325.	Takashi Izawa, Naozumi Ishimaru, Masayuki Kohashi, Rieko Arakaki and Yoshio Hayashi : Crosstalk between RANKL and Fas signaling in dendritic cells controls immune tolerance, 第37回日本免疫学会総会・学術集会ワークショップ, Vol.37, Nov. 2007.
326.	Miho Okuno, Naozumi Ishimaru, Takashi Izawa, Rieko Arakaki, Akiko Yamada and Yoshio Hayashi : Analysis of NF-kB in T cell activation in murine autoimmune model, 第37回日本免疫学会総会・学術集会, Vol.37, 119, Nov. 2007.
327.	Masayuki Kohashi, Naozumi Ishimaru, Akiko Yamada, Rieko Arakaki, Jun Kanno and Yoshio Hayashi : The effect of TCDD administration on murine model for Sjogren's syndrome, 第37回日本免疫学会総会・学術集会, Vol.37, 116, Nov. 2007.
328.	Naozumi Ishimaru : 唾液腺アポトーシスと自己免疫, 日本口腔病理学会総会シンポジウム, Aug. 2007.
329.	Takashi Izawa, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : 関節リウマチモデルMRL/lprマウス樹状細胞の機能解析, 第6回四国免疫フォーラム一般演題, Jul. 2007.
330.	Hiroyoshi Hosokawa, Kazuhito Satomura, Yukihiro Momota, Keiko Kudoh, Seiko Tatehara, Reiko Tokuyama, Hideyuki Takano, Naozumi Ishimaru, Yoshio Hayashi, Masaru Nagayama and 第17回日本口腔粘膜学会 : 口腔白板症の臨床病理学的検討, 第17回日本口腔粘膜学会 2007.7.5∼7.6,東京, Jul. 2007.
331.	Takashi Sakai, Li Liu, Xichuan Teng, Naozumi Ishimaru, Rika Sakai, Nobuya Sano, Ryuji Kaji, Hoang Nam Tran, Yoshio Hayashi and Kiyoshi Fukui : 新規アポトーシス制御分子ヌクリングの肝癌発症機構における役割の解明, 第48回日本生化学会中国四国支部例会, May 2007.
332.	Kohashi Masayuki, Rieko Arakaki, Naozumi Ishimaru and Yoshio Hayashi : シェーグレン症候群モデルマウスにおけるレバミピドの病態抑制効果, 第96回日本病理学会総会, Vol.96, No.1, 295, Mar. 2007.
333.	Rieko Arakaki, Naozumi Ishimaru, Kohashi Masayuki and Yoshio Hayashi : シェーグレン症候群類似RbAp48遺伝子導入マウスにおける病態形成の解析, 第96回日本病理学会総会, Vol.96, No.1, 295, Mar. 2007.
334.	Rieko Arakaki, Naozumi Ishimaru, Masayuki Kohashi and Yoshio Hayashi : シェーグレン症候群類似RbAp48遺伝子導入マウスにおける病態形成の解析, 日本病理学会会誌, Vol.96, No.1, Mar. 2007.
335.	Masayuki Kohashi, Rieko Arakaki, Naozumi Ishimaru and Yoshio Hayashi : シェーグレン症候群モデルマウスにおけるレバミピドの病態抑制効果, 日本病理学会会誌, Vol.96, No.1, Mar. 2007.
336.	Naozumi Ishimaru, 高木篤也, 菅野純 and Yoshio Hayashi : 新生仔マウスへのダイオキシン投与による免疫系への影響, 日本病理学会会誌, Vol.96, No.1, Mar. 2007.
337.	Naozumi Ishimaru, 高木篤也, 菅野純 and Yoshio Hayashi : 新生仔マウスへのダイオキシン投与による免疫系への影響, 第96回日本病理学会総会, Vol.96, No.1, 224, Mar. 2007.
338.	Takashi Izawa, Naozumi Ishimaru, Rieko Arakaki, Keiji Moriyama and Yoshio Hayashi : Immunoregulatory role of RANKL-stimulated dendritic cells on autoimmune arthritis in MRL/lpr mice, 第36回日本免疫学会総会・学術集会ワークショップ, Vol.36, 284, Dec. 2006.
339.	Naozumi Ishimaru, Masayuki Kohashi, Rieko Arakaki, Hidehiro Kishimoto and Yoshio Hayashi : NF-κB2 pathway in T cell activation for autoimmunity, 日本免疫学会総会・学術集会記録, Vol.36, Dec. 2006.
340.	Masayuki Kohashi, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : Effect of rebamipide administration on Sjogren's syndrome mouse model, 日本免疫学会総会・学術集会記録, Vol.36, Dec. 2006.
341.	Rieko Arakaki, Naozumi Ishimaru and Yoshio Hayashi : Development of exocrinopathy resembling Sjogren's syndrome in RbAp48 transgenic mice, 日本免疫学会総会・学術集会記録, Vol.36, Dec. 2006.
342.	Naozumi Ishimaru and Yoshio Hayashi : NF-kBシグナルを介した自己免疫疾患の発症機序, 第54回NPO法人日本口腔科学会, Nov. 2006.
343.	大嶋淳, Takashi Izawa, Naozumi Ishimaru, Yoshio Hayashi and Keiji Moriyama : 関節炎モデルマウスを用いた樹状細胞移入による関節リウマチ病態の修飾, 第65回日本矯正歯科学会大会学術展示, 217, Sep. 2006.
344.	Naozumi Ishimaru, Keisuke Izumi and Yoshio Hayashi : LECラットに発生する炎症性腸疾患の解析, 第3回日本病理学会カンファレンスポスター発表, Aug. 2006.
345.	Yoshio Hayashi, Naozumi Ishimaru and Nobuhiko Katunuma : Cathepsin L-inhibitor Prevents Proinsulin Peptide Processing and Autoimmune Diabetes in Nonobetic(NOD)Mice, Satellite Meeting of the 20th IUBMB International Congress and 11th FAOBMB Congress, Jun. 2006.
346.	Naozumi Ishimaru and Yoshio Hayashi : In Vivo Role of NF-κB-inducing Kinase for T Cell Activation, Satellite Meeting of the 20th IUBMB International Congress and 11th FAOBMB Congress, Jun. 2006.
347.	Rieko Arakaki, Naozumi Ishimaru and Yoshio Hayashi : 臓器特異的アポトーシスと自己免疫, 第5回四国免疫フォーラム一般演題, Jun. 2006.
348.	Naozumi Ishimaru, Hidehiro Kishimoto, Yoshio Hayashi and Sprent Jonathan : T細胞活性化機構におけるNF-kB2経路の役割, 第16回Kyoto T Cell Conference(KTCC) ワークショップ, Jun. 2006.
349.	Naozumi Ishimaru, Keisuke Izumi and Yoshio Hayashi : LECラットに発生する炎症性腸疾患の解析, 第16回LECラット研究会大会, May 2006.
350.	Fumie Omotehara, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : シェーグレン症候群加齢モデルマウスにおける間質性肺病変の解析, 第95回日本病理学会総会一般口演, Vol.95, No.1, 211, May 2006.
351.	Naozumi Ishimaru, Rieko Arakaki, Fumie Omotehara and Yoshio Hayashi : NF-kBシグナルを介した自己免疫疾患の発症機序, 第95回日本病理学会総会一般口演, Vol.95, No.1, 211, May 2006.
352.	Katsushi Miyazaki, Noriaki Takeda, Naozumi Ishimaru and Yoshio Hayashi : 原発性シェーグレン症候群における自己抗原α-フォドリンの生体内での役割の解析, 第107回日本耳鼻咽喉科学会総会, May 2006.
353.	Naozumi Ishimaru, Hidehiro Kishimoto, Jonathan Sprent and Yoshio Hayashi : Immunoregulation by NF-kB for T cell activation in autoimmune disease, 日本免役学会総会·学術集会記録, Vol.35, 275, Dec. 2005.
354.	Naozumi Ishimaru, Hidehiro Kishimoto, Jonathan Sprent and Yoshio Hayashi : Immunoregulation by NF-kB for T cell activation in autoimmune disease, 第35回日本免疫学会総会・学術集会ワークショップ, Vol.35, 275, Dec. 2005.
355.	Takashi Izawa, Naozumi Ishimaru, Fumie Omotehara, Rieko Arakaki, 大嶋淳, Keiji Moriyama and Yoshio Hayashi : RANKL刺激活性化DCを介したMRL/lprマウス関節炎の病態修飾, 第35回日本免疫学会総会・学術集会ワークショップ, Vol.35, 249, Dec. 2005.
356.	Megumi Watanabe, Naozumi Ishimaru, Rieko Arakaki, Fumie Omotehara and Yoshio Hayashi : Niアレルギーにおける樹状細胞及びT細胞の活性化機構, 日本免役学会総会·学術集会記録, Vol.35, 140, Dec. 2005.
357.	Megumi Watanabe, Naozumi Ishimaru, Rieko Arakaki, Fumie Omotehara and Yoshio Hayashi : Niアレルギーにおける樹状細胞及びT細胞の活性化機構, 第35回日本免疫学会総会・学術集会ワークショップ, Vol.35, 140, Dec. 2005.
358.	Fumie Omotehara, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : シェーグレン症候群加齢モデルマウスにおける間質性肺病変の解析, 日本免役学会総会·学術集会記録, Vol.35, 36, Dec. 2005.
359.	小橋真之, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : シェーグレン症候群モデルマウスにおけるレバミピドの治療効果の検討, 日本免役学会総会·学術集会記録, Vol.35, 33, Dec. 2005.
360.	Fumie Omotehara, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : シェーグレン症候群加齢モデルマウスにおける間質性肺病変の解析, 第35回日本免疫学会総会・学術集会ワークショップ, Vol.35, 36, Dec. 2005.
361.	小橋真之, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : シェーグレン症候群モデルマウスにおけるレバミピドの治療効果の検討, 第35回日本免疫学会総会・学術集会ワークショップ, Vol.35, 33, Dec. 2005.
362.	Naozumi Ishimaru : 自己免疫疾患におけるNF-kBを介したT細胞の活性化機構, Journal of Oral Biosciences, Vol.47, 69, Sep. 2005.
363.	Naozumi Ishimaru : 自己免疫疾患におけるNF-kBを介したT 細胞の活性化機構, 第47回歯科基礎医学会学術大会ならびに総会シンポジウム, Vol.47, 69, Sep. 2005.
364.	大嶋淳, Takashi Izawa, Naozumi Ishimaru, Fumie Omotehara, Rieko Arakaki, Keiji Moriyama and Yoshio Hayashi : 樹状細胞移入によるMRL/lprマウス関節リウマチ病態の修飾, 第2回日本病理学会カンファレンスポスター発表, 46, Jul. 2005.
365.	Fumie Omotehara, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : RbAp48トランスジェニックマウスを用いたシェーグレン症候群新規モデルの作成, 第2回日本病理学会カンファレンスポスター発表, 48, Jul. 2005.
366.	Naozumi Ishimaru and Yoshio Hayashi : 自己免疫疾患におけるNF-kBを介したT細胞活性化機構の解析, 第二回日本病理学会カンファレンスポスター発表, 38, Jul. 2005.
367.	Naozumi Ishimaru and Yoshio Hayashi : T細胞活性化機構におけるRelBの役割, 第4回四国免疫フォーラム, Jun. 2005.
368.	Naozumi Ishimaru : 自己免疫疾患におけるNF-kBを介したT細胞活性化機構の解析, 四国歯学会第29回例会・第24回総会帰朝講演, Vol.18, No.2, Jun. 2005. (Tokushima University Institutional Repository) ● Metadata: 263 (Tokushima University Institutional Repository: 263)
369.	Naozumi Ishimaru, Rieko Arakaki, Fumie Omotehara and Yoshio Hayashi : 自己免疫疾患におけるNF-kBを介したT細胞活性化機構の解析, 第94回日本病理学会総会一般口演, Vol.94, No.1, 224, Apr. 2005.
370.	Rieko Arakaki, Naozumi Ishimaru, Fumie Omotehara and Yoshio Hayashi : RbAp48遺伝子導入マウスにみられるシェーグレン症候群類似病変の解析, 第94回日本病理学会総会一般口演, Vol.94, No.1, 206, Apr. 2005.
371.	Fumie Omotehara, Naozumi Ishimaru, Rieko Arakaki, 大嶋淳 and Yoshio Hayashi : シェーグレン症候群における自己抗原120kDa α-フォドリンの意義, 第94回日本病理学会総会一般口演, Vol.94, No.1, 206, Apr. 2005.
372.	Jun Oshima, Naozumi Ishimaru, Rieko Arakaki, Fumie Omotehara and Yoshio Hayashi : RANKL刺激樹状細胞移入によるMRL/lprマウス関節リウマチ病変の解析, 第94回日本病理学会総会一般口演, Vol.94, No.1, 197, Apr. 2005.
373.	Takashi Izawa, Naozumi Ishimaru, Rieko Arakaki and Yoshio Hayashi : RANKL刺激樹状細胞移入によるMRL/lprマウス自己免疫性関節炎の病態修飾, 第33回日本免疫学会総会・学術集会ワークショップ, Dec. 2003.
374.	日比弓紀子, Kenji Fujisawa, Tetsuya Yuasa, Naozumi Ishimaru and Masaru Nagayama : 歯肉増殖を伴ったSturge-Weber症候群の1例, 第49回日本口腔科学会中国・四国地方部会, 2001. (Summary) 1
375.	Yoshiko Noda, Yukihiro Momota, Kazuhito Satomura, 鎌田伸之, Naozumi Ishimaru and Masaru Nagayama : 上顎洞に発症したアスペルギルス症の1例 : 血清学的検査の有用性についての考察, 第45回日本口腔外科学会総会, Oct. 2000.
376.	Yukihiro Momota, Yoshiko Noda, Kazuhito Satomura, Nobuyuki Kamata, Masaru Nagayama and Naozumi Ishimaru : 上顎洞に発症したアスペルギルス症の2例-PCR法を用いた遺伝子診断-, 第45回日本口腔外科学会総会, 2000.

Et cetera, Workshop:

1.	木曽田暁, 邵文華, Takaaki Tsunematsu, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : 口腔癌における上皮-間葉移行の関与, 徳島県歯科医学大会(四国歯学会第56回例会), Feb. 2020.
2.	邵文華, Takaaki Tsunematsu, 梅田将旭, 木曽田暁, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : 口腔癌の進展に関わる新規ペリオスチンスプライシングバリアントの同定, 徳島県歯科医学大会(四国歯学会第56回例会), Feb. 2020.
3.	林亜門, 清水朱里, 中西美緒, 山内加奈, Mami Sato, 邵文華, 木曽田暁, Hitomi Fukui, 木野倫子, Aya Ushio, Akiko Yamada, Takaaki Tsunematsu, Rieko Arakaki, Yasusei Kudo and Naozumi Ishimaru : 口腔分子病態学分野における免疫・癌研究, 徳島県歯科医学大会(四国歯学会第56回例会), Feb. 2020.
4.	Takaaki Tsunematsu, Naozumi Ishimaru and Yasusei Kudo : 染色体パッセンジャー複合体による多能性幹細胞の未分化能維持機構, 第37回染色体ワークショップ・第18回核ダイナミクス研究会, Dec. 2019.
5.	Takaaki Tsunematsu, Naozumi Ishimaru and Yasusei Kudo : 染色体パッセンジャー複合体によるAurora-B活性を介した多能性幹細胞の未分化能維持機構, 第16回日本病理学会カンファレンス, Aug. 2019.
6.	Naofumi Tamaki, 陳舒, Yasusei Kudo, Kaname Miki, Naozumi Ishimaru and Hiro-O Ito : 実験的口腔粘膜モデルにおけるレスベラトロールの抗酸化・抗炎症効果, 第38回分子病理研究会, Jul. 2019.
7.	Satoru Kisoda, Bunka Sho, Aya Ushio, Mami Sato, Rieko Arakaki, Naozumi Ishimaru and Yasusei Kudo : 口腔癌におけるpartial-EMTに関連する遺伝子の悪性度への関与, 第38回分子病理学研究会, Jul. 2019.
8.	Natsumi Fujiwara, Wenhua Shao, Kaya Yoshida, Rieko Arakaki, Kazumi Ozaki, Naozumi Ishimaru and Yasusei Kudo : Fusobacterium nucleatumが与える口腔癌細胞への影響, 第38回分子病理学研究会淡路島シンポジウム(兵庫県) 2019年7月19-20日, Jul. 2019.
9.	Takashi Izawa, Rieko Arakaki, Eiji Tanaka and Naozumi Ishimaru : Crosstalk between cytokine RANKL and AhR signaling in osteoclasts controls bone homeostasis, Gordon Research Seminar; "Bones and Teeth" Translating Mechanisms of Bone Formation and Repair, Jan. 2018. (Keyword) osteoclast / RANKL
10.	S. Afroz, Iwasa Takuma, Oshima Masamitsu, Rieko Arakaki, Miho Inoue, Naozumi Ishimaru and Yoshizo Matsuka : Cytokine release from satellite glial cells of trigeminal ganglia, Tokushima University Bioscience Retreat, Sep. 2017.
11.	Keiko Aota, Yoshiko Yamamura, Katsumi Motegi, Naozumi Ishimaru and Masayuki Azuma : シェーグレン症候群患者に対するセファランチンの有効性に関する臨床病理学的研究, Shikoku Dental Research, Mar. 2012.
12.	Naozumi Ishimaru and Yoshio Hayashi : 臓器特異的アポトーシスとシェーグレン症候群, 第15回日本シェーグレン症候群研究会, Sep. 2006.

Report:

1.	Yoshihiko Ueno, Yosuke Seki, Satoshi Kinugawa, Hisayoshi Morioka, Akira Takahashi, Kenji Mori, Naozumi Ishimaru, Kazumi Ozaki, Tetsuo Yamazaki, Atsushi Takada, Yoshihiro Uto, Takahito Saito and Maiko Kamioka : 令和4年度徳島大学高等教育研究センターアドミッション部門報告書, 令和4年度徳島大学高等教育研究センターアドミッション部門報告書, Mar. 2023.
2.	Yoshihiko Ueno, Yosuke Seki, Ryuji Yorioka, Yuishin Izumi, Takeshi Nikawa, Reiko Okahisa, Naozumi Ishimaru, Kazumi Ozaki, Hideji TANAKA, Kenji Terada, Tamotsu Tanaka, Ray S. Furuya and Maiko Kamioka : 令和3年度徳島大学高等教育研究センターアドミッション部門報告書, 令和3年度徳島大学高等教育研究センターアドミッション部門報告書, Mar. 2022.
3.	Jonathan Sprent, Onur Boyman, Jea Hoe Cho, Naozumi Ishimaru, Hidehiro Kishimoto, M Kovar, DC Lenz, MP Rubinstein and X Shen : The Thymus and T-Cell Specificity, The Scripps Research Institute Scientific Report, Vol.30, 141-142, Sep. 2005.

Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)

IgG4関連疾患の疾患特異的自己抗原の同定 -新たな診断方法と治療薬の開発- (Project/Area Number: 23KK0164 )
Clinical application based on the molecular mechanism of autoantibody production in autoimmunity (Project/Area Number: 23K18361 )
Novel pathogenesis and therapeutic strategy of autoimmunity based on immune-tuning molecules (Project/Area Number: 23H00438 )
New molecular mechanism of autoimmunity via deficiency in mucin glycosylation of salivary gland (Project/Area Number: 21K19605 )
Common molecular mechanisms underlying age- and autoimmune-related disturbance of salivary secretion (Project/Area Number: 21H03115 )
Establishment of novel oral cancer stem cell model mimicking human oral cancer by reprogramming and insertion of gene mutation (Project/Area Number: 19H03853 )
Analysis of Pathogenesis of Autoimmunity through Communication between Organs (Project/Area Number: 19H01070 )
Molecular Mechanism of Autoimmune Germinal Center Reaction and a New Therapeutic Strategy for Autoimmunity (Project/Area Number: 18K19648 )
Study on the generation of oral cancer stem cell and analysis of its nature (Project/Area Number: 17K19760 )
Development of a novel treatment method for xerostomia by dental pulp stem cell-derived humoral factor (Project/Area Number: 17H04404 )
Clarification of the mechanism of oral carcinogenesis by the defect of degradation of chromosome passenger complex protein (Project/Area Number: 16H05542 )
Analysis of autoimmunity caused by environmental factors~New pathogenesis of autoimmune disease~ (Project/Area Number: 16H02690 )
Explore for master regulator of EMT in oral cancer (Project/Area Number: 15K15740 )
Development of diagnostic techniques specific for Sjogren's syndrome by estrogen-related molecules (Project/Area Number: 15K15676 )
Analysis of molecular mechanisms of sensitization phase to develop effective treatments against metal allergy (Project/Area Number: 15H05028 )
新規バイオマーカーを用いたシェーグレン症候群の確定診断法の開発 (Project/Area Number: 22659342 )
The analysis of Ni allergy development and the therapeutic strategy in prosthodontics (Project/Area Number: 21390518 )
自己免疫疾患における標的臓器と免疫ネットワークの解明と新規治療法の開発 (Project/Area Number: 21390503 )
Immunotherapeutic analysis using newly established murine models for Sjogren' s syndrome (Project/Area Number: 21249090 )
Effect of estrogen deficiency on the development of autoimmune diseases (Project/Area Number: 20390479 )
調節性T細胞を制御する新規免疫調節機構の解明 (Project/Area Number: 19659491 )
Effect of Sex Hormone on the Development of Autoimmune Diseases (Project/Area Number: 18390498 )
自己免疫疾患におけるNF-κBを介したT細胞活性化機構の解析 (Project/Area Number: 17689049 )
Molecular analysis of pathogenesis on Sjogren's syndrome and its application of new diagnosis and therapy (Project/Area Number: 17109016 )
Fasリガンド分子制御によるシェーグレン症候群治療法の研究開発 (Project/Area Number: 15659094 )
自己免疫疾患におけるエストロジェンを介したアポトーシス調節機構の解析 (Project/Area Number: 12771086 )
自己免疫疾患老化モデルにおけるp16の解析 (Project/Area Number: 12671826 )
Search by Researcher Number (60314879)