徳島大学 / 教育研究者総覧 --- 毛利安宏

個人のホームページ

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

専門分野

○	免疫学 (Immunology)

研究テーマ

○	自己免疫疾患発症のメカニズムに関する研究 (自己免疫 (autoimmunity), 胸腺 (thymus))

著書・論文

学術論文(審査論文):

1.	Kumiko Kamada, Naito Kurio, Yasuhiro Mouri and Yasusei Kudo : Combination treatment with hyaluronic acid synthesis and Bcl-2 inhibitors induces senolytic elimination of oral squamous cell carcinoma cells in vitro., Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 2024.
2.	Motoharu Sarubo, Yasuhiro Mouri, Akira Moromizato, Azusa Yamada, Shengjan Jin, Wenhua Shao, Hiroko Hagita, Keiko Miyoshi and Yasusei Kudo : Involvement of TGFBI-TAGLN axis in cancer stem cell property of head and neck squamous cell carcinoma., Scientific Reports, Vol.14, No.1, 6767, 2024. (要約) Head and neck squamous cell carcinoma (HNSCC) is a significant healthcare burden globally. Previous research using single-cell transcriptome analysis identified TGFBI as a crucial marker for the partial-epithelial-mesenchymal transition (partial-EMT) program. However, the precise role of TGFBI in HNSCC progression remains unclear. Therefore, our study aimed to clarify the impact of TGFBI on the malignant behavior of HNSCC cells. Through RNA-sequencing data from the TCGA database, we validated that increased TGFBI expression correlates with a higher occurrence of lymph node metastasis and unfavorable prognosis in HNSCC cases. Functional experiments demonstrated that TGFBI overexpression enhances the ability of sphere formation, indicating stem-cell-like properties. Conversely, TGFBI depletion reduces sphere formation and suppresses the expression of cancer stem cell (CSC) markers. RNA-sequencing analysis of TGFBI-overexpressing and control HNSCC cells revealed TAGLN as a downstream effector mediating TGFBI-induced sphere formation. Remarkably, TAGLN depletion abolished TGFBI-induced sphere formation, while its overexpression rescued the suppressed sphere formation caused by TGFBI depletion. Moreover, elevated TAGLN expression showed correlations with the expression of TGFBI and partial-EMT-related genes in HNSCC cases. In conclusion, our findings suggest that TGFBI may promote CSC properties through the upregulation of TAGLN. These novel insights shed light on the involvement of the TGFBI-TAGLN axis in HNSCC progression and hold implications for the development of targeted therapies. (キーワード) Humans / Squamous Cell Carcinoma of Head and Neck / Carcinoma, Squamous Cell / Head and Neck Neoplasms / Cell Line, Tumor / Neoplastic Stem Cells / Epithelial-Mesenchymal Transition / RNA (RNA) / Gene Expression Regulation, Neoplastic (徳島大学機関リポジトリ) ● Metadata: 119243 (出版サイトへのリンク) ● Publication site (DOI): 10.1038/s41598-024-57478-0 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38514830 ● Summary page in Scopus @ Elsevier: 2-s2.0-85188230546 (徳島大学機関リポジトリ: 119243, DOI: 10.1038/s41598-024-57478-0, PubMed: 38514830, Elsevier: Scopus)
3.	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. (要約) In HNSCC patients, USP10, USP14, OTUB1, and STAMBP among the screened DUBs were associated with a poor prognosis. Among them, OTUB1 showed the most aggressive characteristics in both in vitro and in vivo experiments. Additionally, OTUB1 regulated the stability and nuclear localization of YAP1, a substrate involved in cell proliferation and invasion. Notably, OTUB1 expression exhibited a positive correlation with the HNSCC-YAP score in HNSCC cells. (キーワード) deubiquitinating enzyme (DUB) / head and neck squamous cell carcinoma / invasion / OTUB1 / YAP (徳島大学機関リポジトリ) ● Metadata: 118778 (出版サイトへのリンク) ● Publication site (DOI): 10.1002/cam4.6735 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37986681 ● CiNii @ 国立情報学研究所 (CRID): 1940583859514191616 ● Summary page in Scopus @ Elsevier: 2-s2.0-85177448617 (徳島大学機関リポジトリ: 118778, DOI: 10.1002/cam4.6735, PubMed: 37986681, CiNii: 1940583859514191616, Elsevier: Scopus)
4.	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. (要約) 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. (徳島大学機関リポジトリ) ● Metadata: 118312 (出版サイトへのリンク) ● Publication site (DOI): 10.1002/cam4.5601 (文献検索サイトへのリンク) ● 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 (徳島大学機関リポジトリ: 118312, DOI: 10.1002/cam4.5601, PubMed: 36691359)
5.	Yoshiko Yamamura, Keiko Miyoshi, Yasuhiro Mouri, Yasusei Kudo and Youji Miyamoto : miR 155 5p can be involved in acquisition of osseointegration on titanium surface, In Vitro Cellular & Developmental Biology. Animal, Vol.58, No.8, 693-701, 2022. (要約) Dental implants made of titanium are commonly used. Although titanium implants succeed by osseointegration with bone, the detailed molecular mechanism of osseointegration is unclear. To clarify the involvement of microRNA (miRNA) in the acquisition of osseointegration on titanium, here we compared the miRNA expression profiles of mouse osteoblast-like cells (MC3T3-E1) cultured on titanium-, gold-, and stainless steel-coating glass dishes by microarray analysis. Three kinds of metals, namely titanium, gold, and stainless steel, were coated on the surface of the glass dishes by sputtering with similar roughness and shape of their surface. After MC3T3-E1 cells were cultured on the dishes without coating or coating with titanium, gold, or stainless steel for 6 h, total RNA was extracted, and miRNA expression was analyzed by microarray. To confirm the expression of the selected miRNA during osteogenic differentiation of MC3T3-E1 cells, real-time PCR analysis was performed. Furthermore, the effects of selected miRNA were examined by ectopic overexpression in MC3T3-E1 cells. The microarray analysis revealed that the expressions of miR-155-5p and miR-7023-3p were significantly increased in MC3T3-E1 cells cultured on titanium-coating glass dishes, compared to non-coating, gold-, and stainless steel-coating glass dishes. Interestingly, miR-155-5p was upregulated during osteogenic differentiation of MC3T3-E1 cells. Furthermore, overexpression of miR-155-5p enhanced the expression of Runx2 and Col1a1. In this study, miR-155-5p may be involved in the acquisition of osseointegration on titanium implant via upregulating osteogenic differentiation-related genes. (出版サイトへのリンク) ● Publication site (DOI): 10.1007/s11626-022-00718-2 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36053380 ● Search Scopus @ Elsevier (PMID): 36053380 ● Search Scopus @ Elsevier (DOI): 10.1007/s11626-022-00718-2 (DOI: 10.1007/s11626-022-00718-2, PubMed: 36053380)
6.	Satoru Kisoda, Yasuhiro Mouri, Naoya Kitamura, Tetsuya Yamamoto, Keiko Miyoshi and Yasusei Kudo : The role of partial-EMT in the progression of head and neck squamous cell carcinoma., Journal of Oral Biosciences, Vol.64, No.2, 176-182, 2022. (要約) In this review, we highlight the features of partial-EMT in HNSCC by summarizing previous studies. Moreover, we discuss the therapeutic potential for targeting partial-EMT. (キーワード) Carcinoma, Squamous Cell / Epithelial-Mesenchymal Transition / Head and Neck Neoplasms / Humans / Lymphatic Metastasis / Squamous Cell Carcinoma of Head and Neck (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.job.2022.02.004 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35176487 ● Summary page in Scopus @ Elsevier: 2-s2.0-85125440565 (DOI: 10.1016/j.job.2022.02.004, PubMed: 35176487, Elsevier: Scopus)
7.	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. (要約) 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. (徳島大学機関リポジトリ) ● Metadata: 116445 (出版サイトへのリンク) ● Publication site (DOI): 10.1038/s41598-021-94384-1 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34294795 ● Summary page in Scopus @ Elsevier: 2-s2.0-85111135598 (徳島大学機関リポジトリ: 116445, DOI: 10.1038/s41598-021-94384-1, PubMed: 34294795, Elsevier: Scopus)
8.	Go Ohe, Yasusei Kudo, Kumiko Kamada, Yasuhiro Mouri, Natsumi Takamaru, Keiko Kudoh, Naito Kurio and Youji Miyamoto : Soluble Factor from Oral Cancer Cell Lines Inhibits Interferon-γ Production by OK-432 via CD40/CD40Ligand Pathway, Cancers, Vol.13, No.13, 2021. (徳島大学機関リポジトリ) ● Metadata: 116508 (出版サイトへのリンク) ● Publication site (DOI): 10.3390/cancers13133301 (文献検索サイトへのリンク) ● Summary page in Scopus @ Elsevier: 2-s2.0-85108890231 (徳島大学機関リポジトリ: 116508, DOI: 10.3390/cancers13133301, Elsevier: Scopus)
9.	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. (要約) 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. (徳島大学機関リポジトリ) ● Metadata: 114969 (出版サイトへのリンク) ● Publication site (DOI): 10.1111/odi.13351 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32277532 ● Summary page in Scopus @ Elsevier: 2-s2.0-85083974773 (徳島大学機関リポジトリ: 114969, DOI: 10.1111/odi.13351, PubMed: 32277532, Elsevier: Scopus)
10.	Hitoshi Nishijima, Tatsuya Kajimoto, Yoshiki Matsuoka, Yasuhiro Mouri, Junko Morimoto, Minoru Matsumoto, Hiroshi Kawano, Yasuhiko Nishioka, Hisanori Uehara, Keisuke Izumi, Koichi Tsuneyama, Il-mi Okazaki, Taku Okazaki, Kazuyoshi Hosomichi, Ayako Shiraki, Makoto Shibutani, Kunitoshi Mitsumori and Mitsuru Matsumoto : Paradoxical development of polymyositis-like autoimmunity through augmented expression of autoimmune regulator (AIRE)., Journal of Autoimmunity, Vol.86, 75-92, 2018. (要約) Autoimmunity is prevented by the function of the autoimmune regulator [AIRE (Aire in mice)], which promotes the expression of a wide variety of tissue-restricted antigens (TRAs) from medullary thymic epithelial cells (mTECs) and from a subset of peripheral antigen-presenting cells (APCs). We examined the effect of additive expression of human AIRE (huAIRE) in a model of autoimmune diabetes in NOD mice. Unexpectedly, we observed that mice expressing augmented AIRE/Aire developed muscle-specific autoimmunity associated with incomplete maturation of mTECs together with impaired expression of Aire-dependent TRAs. This led to failure of deletion of autoreactive T cells together with dramatically reduced production of regulatory T cells in the thymus. In peripheral APCs, expression of costimulatory molecules was augmented. We suggest that levels of Aire expression need to be tightly controlled for maintenance of immunological tolerance. Our results also highlight the importance of coordinated action between central tolerance and peripheral tolerance under the common control of Aire. (徳島大学機関リポジトリ) ● Metadata: 112347 (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.jaut.2017.09.006 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28931462 ● Search Scopus @ Elsevier (PMID): 28931462 ● Search Scopus @ Elsevier (DOI): 10.1016/j.jaut.2017.09.006 (徳島大学機関リポジトリ: 112347, DOI: 10.1016/j.jaut.2017.09.006, PubMed: 28931462)
11.	Yasuhiro Mouri, Yoshihiro Ueda, Tomoyoshi Yamano, Minoru Matsumoto, Koichi Tsuneyama, Tatsuo Kinashi and Mitsuru Matsumoto : Mode of tolerance induction and requirement for Aire are governed by the cell types that express self-antigen and those that present antigen, The Journal of Immunology, Vol.199, No.12, 3959-3971, 2017. (要約) Aire controls the fate of autoreactive thymocytes (i.e., clonal deletion or development into regulatory T cells [Tregs]) through transcriptional control of the expression of tissue-restricted self-antigens (TRAs) from medullary thymic epithelial cells (mTECs) and bone marrow (BM)-derived cells. Although TRAs expressed by mTECs and BM-derived cells are suggested to complement each other to generate a full spectrum of TRAs, little is known about the relative contribution of TRAs from each component for establishment of self-tolerance. Furthermore, the precise role of Aire in specific types of Aire-expressing APCs remains elusive. We have approached these issues by generating two different types of transgenic mouse (Tg) model, which express a prefixed model self-antigen driven by the insulin promoter or the Aire promoter. In the insulin-promoter Tg model, mTECs alone were insufficient for clonal deletion, and BM-derived APCs were required for this action by utilizing Ag transferred from mTECs. In contrast, mTECs alone were able to induce Tregs, although at a much lower efficiency in the absence of BM-derived APCs. Importantly, lack of Aire in mTECs, but not in BM-derived APCs, impaired both clonal deletion and production of Tregs. In the Aire-promoter Tg model, both mTECs and BM-derived APCs could independently induce clonal deletion without Aire, and production of Tregs was impaired by the lack of Aire in mTECs, but not in BM-derived APCs. These results suggest that the fate of autoreactive thymocytes together with the requirement for Aire depend on the cell types that express self-antigens and the types of APCs involved in tolerance induction. (キーワード) Animals / Antigen Presentation / Antigen-Presenting Cells / Autoantigens / Clonal Deletion / Epithelial Cells / Female / Gene Expression Regulation / Gene Knock-In Techniques / Genes, Synthetic / インスリン (insulin) / Male / Mice / Mice, Inbred C57BL / ノックアウトマウス (knockout mice) / Mice, Transgenic / Ovalbumin / Promoter Regions, Genetic / Rats / Specific Pathogen-Free Organisms / T-Lymphocytes, Regulatory / Thymus Gland / Transcription Factors / Transgenes (出版サイトへのリンク) ● Publication site (DOI): 10.4049/jimmunol.1700892 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29101311 ● Summary page in Scopus @ Elsevier: 2-s2.0-85038566360 (DOI: 10.4049/jimmunol.1700892, PubMed: 29101311, Elsevier: Scopus)
12.	Hiroshi Kawano, Hitoshi Nishijima, Junko Morimoto, Fumiko Hirota, Ryoko Morita, Yasuhiro Mouri, Yasuhiko Nishioka and Mitsuru Matsumoto : Aire expression is inherent to most medullary thymic epithelial cells during their differentiation program., The Journal of Immunology, Vol.195, No.11, 5149-5158, 2015. (要約) Aire in medullary thymic epithelial cells (mTECs) plays an important role in the establishment of self-tolerance. Because Aire+ mTECs appear to be a limited subset, they may constitute a unique lineage(s) among mTECs. An alternative possibility is that all mTECs are committed to express Aire in principle, but Aire expression by individual mTECs is conditional. To investigate this issue, we established a novel Aire reporter strain in which endogenous Aire is replaced by the human AIRE-GFP-Flag tag (Aire/hAGF-knockin) fusion gene. The hAGF reporter protein was produced and retained very efficiently within mTECs as authentic Aire nuclear dot protein. Remarkably, snapshot analysis revealed that mTECs expressing hAGF accounted for >95% of mature mTECs, suggesting that Aire expression does not represent a particular mTEC lineage(s). We confirmed this by generating Aire/diphtheria toxin receptor knockin mice in which long-term ablation of Aire+ mTECs by diphtheria toxin treatment resulted in the loss of most mature mTECs beyond the proportion of those apparently expressing Aire. These results suggest that Aire expression is inherent to all mTECs but may occur at particular stage(s) and/or cellular states during their differentiation, thus accounting for the broad impact of Aire on the promiscuous gene expression of mTECs. (徳島大学機関リポジトリ) ● Metadata: 109688 (出版サイトへのリンク) ● Publication site (DOI): 10.4049/jimmunol.1501000 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26503950 ● Search Scopus @ Elsevier (PMID): 26503950 ● Search Scopus @ Elsevier (DOI): 10.4049/jimmunol.1501000 (徳島大学機関リポジトリ: 109688, DOI: 10.4049/jimmunol.1501000, PubMed: 26503950)
13.	Hitoshi Nishijima, Satsuki Kitano, Hitoshi Miyachi, Junko Morimoto, Hiroshi Kawano, Fumiko Hirota, Ryoko Morita, Yasuhiro Mouri, Kiyoshi Masuda, Issei Imoto, Koichi Ikuta and Mitsuru Matsumoto : Ectopic Aire expression in the thymic cortex reveals inherent properties of Aire as a tolerogenic factor within the medulla., The Journal of Immunology, Vol.195, No.10, 4641-4649, 2015. (要約) Cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells (mTECs) play essential roles in the positive and negative selection of developing thymocytes, respectively. Aire in mTECs plays an essential role in the latter process through expression of broad arrays of tissue-restricted Ags. To determine whether the location of Aire within the medulla is absolutely essential or whether Aire could also function within the cortex for establishment of self-tolerance, we used bacterial artificial chromosome technology to establish a semiknockin strain of NOD-background (β5t/Aire-transgenic) mice expressing Aire under control of the promoter of β5t, a thymoproteasome expressed exclusively in the cortex. Although Aire was expressed in cTECs as typical nuclear dot protein in β5t/Aire-Tg mice, cTECs expressing Aire ectopically did not confer transcriptional expression of either Aire-dependent or Aire-independent tissue-restricted Ag genes. We then crossed β5t/Aire-Tg mice with Aire-deficient NOD mice, generating a strain in which Aire expression was confined to cTECs. Despite the presence of Aire(+) cTECs, these mice succumbed to autoimmunity, as did Aire-deficient NOD mice. The thymic microenvironment harboring Aire(+) cTECs, within which many Aire-activated genes were present, also showed no obvious alteration of positive selection, suggesting that Aire's unique property of generating a self-tolerant T cell repertoire is functional only in mTECs. (出版サイトへのリンク) ● Publication site (DOI): 10.4049/jimmunol.1501026 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26453754 ● Summary page in Scopus @ Elsevier: 2-s2.0-84951861488 (DOI: 10.4049/jimmunol.1501026, PubMed: 26453754, Elsevier: Scopus)
14.	Yasuhiro Mouri, Hitoshi Nishijima, Hiroshi Kawano, Fumiko Hirota, Nobuo Sakaguchi, Junko Morimoto and Mitsuru Matsumoto : NF-κB-Inducing Kinase in Thymic Stroma Establishes Central Tolerance by Orchestrating Cross-Talk with Not Only Thymocytes but Also Dendritic Cells., The Journal of Immunology, Vol.193, No.9, 4356-4367, 2014. (要約) Essential roles of NF-κB-inducing kinase (NIK) for the development of medullary thymic epithelial cells (mTECs) and regulatory T cells have been highlighted by studies using a strain of mouse bearing a natural mutation of the NIK gene (aly mice). However, the exact mechanisms underlying the defect in thymic cross-talk leading to the breakdown of self-tolerance in aly mice remain elusive. In this study, we demonstrated that production of regulatory T cells and the final maturation process of positively selected conventional αβ T cells are impaired in aly mice, partly because of a lack of mature mTECs. Of note, numbers of thymic dendritic cells and their expression of costimulatory molecules were also affected in aly mice in a thymic stroma-dependent manner. The results suggest a pivotal role of NIK in the thymic stroma in establishing self-tolerance by orchestrating cross-talk between mTECs and dendritic cells as well as thymocytes. In addition, we showed that negative selection was impaired in aly mice as a result of the stromal defect, which accounts for the development of organ-specific autoimmunity through a lack of normal NIK. (出版サイトへのリンク) ● Publication site (DOI): 10.4049/jimmunol.1400389 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25261487 ● Search Scopus @ Elsevier (PMID): 25261487 ● Search Scopus @ Elsevier (DOI): 10.4049/jimmunol.1400389 (DOI: 10.4049/jimmunol.1400389, PubMed: 25261487)
15.	Yumiko Nishikawa, Hitoshi Nishijima, Minoru Matsumoto, Junko Morimoto, Fumiko Hirota, Satoru Takahashi, Hervé Luche, Joerg Hans Fehring, Yasuhiro Mouri and Mitsuru Matsumoto : Temporal lineage tracing of Aire-expressing cells reveals a requirement for Aire in their maturation program., The Journal of Immunology, Vol.192, No.6, 2585-2592, 2014. (要約) Understanding the cellular dynamics of Aire-expressing lineage(s) among medullary thymic epithelial cells (AEL-mTECs) is essential for gaining insight into the roles of Aire in establishment of self-tolerance. In this study, we monitored the maturation program of AEL-mTECs by temporal lineage tracing, in which bacterial artificial chromosome transgenic mice expressing tamoxifen-inducible Cre recombinase under control of the Aire regulatory element were crossed with reporter strains. We estimated that the half-life of AEL-mTECs subsequent to Aire expression was ∼7-8 d, which was much longer than that reported previously, owing to the existence of a post-Aire stage. We found that loss of Aire did not alter the overall lifespan of AEL-mTECs, inconsistent with the previous notion that Aire expression in medullary thymic epithelial cells (mTECs) might result in their apoptosis for efficient cross-presentation of self-antigens expressed by AEL-mTECs. In contrast, Aire was required for the full maturation program of AEL-mTECs, as exemplified by the lack of physiological downregulation of CD80 during the post-Aire stage in Aire-deficient mice, thus accounting for the abnormally increased CD80(high) mTECs seen in such mice. Of interest, increased CD80(high) mTECs in Aire-deficient mice were not mTEC autonomous and were dependent on cross-talk with thymocytes. These results further support the roles of Aire in the differentiation program of AEL-mTECs. (キーワード) Animals / Antigens, CD80 / Apoptosis / Autoantigens / Cell Differentiation / Cell Lineage / Cells, Cultured / Cross-Priming / Epithelial Cells / Flow Cytometry / Immunohistochemistry / Kinetics / Luminescent Proteins / Mice / Mice, Inbred C57BL / Mice, Knockout / Mice, Transgenic / Thymocytes / Thymus Gland / Time Factors / Transcription Factors (出版サイトへのリンク) ● Publication site (DOI): 10.4049/jimmunol.1302786 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24516201 ● Summary page in Scopus @ Elsevier: 2-s2.0-84897508383 (DOI: 10.4049/jimmunol.1302786, PubMed: 24516201, Elsevier: Scopus)
16.	Sumiko Yoshida, Ken-ichi Aihara, Yasumasa Ikeda, Yuka Sumitomo-Ueda, Ryoko Uemoto, Kazue Ishikawa, Takayuki Ise, Shusuke Yagi, Takashi Iwase, Yasuhiro Mouri, Matomo Sakari, Takahiro Matsumoto, Ken-ichi Takeyama, Masashi Akaike, Mitsuru Matsumoto, Masataka Sata, Kenneth Walsh, Shigeaki Kato and Toshio Matsumoto : Androgen receptor promotes sex-independent angiogenesis in response to ischemia and is required for activation of vascular endothelial growth factor receptor signaling., Circulation, Vol.128, No.1, 60-71, 2013. (要約) These results document a physiological role of AR in sex-independent angiogenic potency and provide evidence of novel cross-talk between the androgen/AR signaling and VEGF/kinase insert domain protein receptor signaling pathways. (出版サイトへのリンク) ● Publication site (DOI): 10.1161/CIRCULATIONAHA.113.001533 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23723256 ● Search Scopus @ Elsevier (PMID): 23723256 ● Search Scopus @ Elsevier (DOI): 10.1161/CIRCULATIONAHA.113.001533 (DOI: 10.1161/CIRCULATIONAHA.113.001533, PubMed: 23723256)
17.	Yasuhiro Mouri, Masashi Yano, Miho Shinzawa, Yusuke Shimo, Fumiko Hirota, Yumiko Nishikawa, Takuro Nii, Hiroshi Kiyonari, Takaya Abe, Hisanori Uehara, Keisuke Izumi, Koji Tamada, Lieping Chen, Josef M. Penninger, Jun-ichiro Inoue, Taishin Akiyama and Mitsuru Matsumoto : Lymphotoxin signal promotes thymic organogenesis by eliciting RANK expression in the embryonic thymic stroma, The Journal of Immunology, Vol.186, No.9, 5047-5057, 2011. (要約) It has recently become clear that signals mediated by members of the TNFR superfamily, including lymphotoxin-β receptor (LTβR), receptor activator for NF-κB (RANK), and CD40, play essential roles in organizing the integrity of medullary thymic epithelial cells (mTECs) required for the establishment of self-tolerance. However, details of the mechanism responsible for the unique and cooperative action of individual and multiple TNFR superfamily members during mTEC differentiation still remain enigmatic. In this study, we show that the LTβR signal upregulates expression of RANK in the thymic stroma, thereby promoting accessibility to the RANK ligand necessary for mTEC differentiation. Cooperation between the LTβR and RANK signals for optimal mTEC differentiation was underscored by the exaggerated defect of thymic organogenesis observed in mice doubly deficient for these signals. In contrast, we observed little cooperation between the LTβR and CD40 signals. Thus, the LTβR signal exhibits a novel and unique function in promoting RANK activity for mTEC organization, indicating a link between thymic organogenesis mediated by multiple cytokine signals and the control of autoimmunity. (キーワード) Animals / Antigens, CD40 / 細胞分化 (cell differentiation) / Embryo, Mammalian / Epithelial Cells / Flow Cytometry / 遺伝子発現 (gene expression) / Gene Expression Regulation / 免疫組織化学 (immunohistochemistry) / Lymphotoxin beta Receptor / Mice / Mice, Knockout / Organogenesis / Receptor Activator of Nuclear Factor-kappa B / Reverse Transcriptase Polymerase Chain Reaction / Self Tolerance / シグナル伝達 (signal transduction) / Thymus Gland (出版サイトへのリンク) ● Publication site (DOI): 10.4049/jimmunol.1003533 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21441458 ● Search Scopus @ Elsevier (PMID): 21441458 ● Search Scopus @ Elsevier (DOI): 10.4049/jimmunol.1003533 (DOI: 10.4049/jimmunol.1003533, PubMed: 21441458)
18.	Yumiko Nishikawa, Fumiko Hirota, Masashi Yano, Kitajima Hiroyuki, Miyazaki Jun-ichi, Kawamoto Hiroshi, Yasuhiro Mouri and Mitsuru Matsumoto : Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation, The Journal of Experimental Medicine, Vol.207, No.5, 963-971, 2010. (要約) The roles of autoimmune regulator (Aire)-expressing medullary thymic epithelial cells (mTECs) in the organization of the thymic microenvironment for establishing self-tolerance are enigmatic. We sought to monitor the production and maintenance of Aire-expressing mTECs by a fate-mapping strategy in which bacterial artificial chromosome transgenic (Tg) mice expressing Cre recombinase under the control of the Aire regulatory element were crossed with a GFP reporter strain. We found that, in addition to its well recognized expression within mature mTECs, Aire was expressed in the early embryo before emergence of the three germ cell layers. This observation may help to explain the development of ectodermal dystrophy often seen in patients with AIRE deficiency. With the use of one Tg line in which Cre recombinase expression was confined to mTECs, we found that Aire(+)CD80(high) mTECs further progressed to an Aire(-)CD80(intermediate) stage, suggesting that Aire expression is not constitutive from after its induction until cell death but instead is down-regulated at the beginning of terminal differentiation. We also demonstrated that many mTECs of Aire-expressing lineage are in close contact with thymic dendritic cells. This close proximity may contribute to transfer of tissue-restricted self-antigens expressed by mTECs to professional antigen-presenting cells. (キーワード) Animals / Cell Differentiation / Embryonic Development / Epithelial Cells / Gene Expression Regulation / Genes, Reporter / Green Fluorescent Proteins / Lymphoid Tissue / Male / Mice / Mice, Transgenic / Spermatogenesis / Testis / Thymus Gland / Transcription Factors (出版サイトへのリンク) ● Publication site (DOI): 10.1084/jem.20092144 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20404099 ● Search Scopus @ Elsevier (PMID): 20404099 ● Search Scopus @ Elsevier (DOI): 10.1084/jem.20092144 (DOI: 10.1084/jem.20092144, PubMed: 20404099)
19.	Masashi Yano, Noriyuki Kuroda, Hongwei Han, Makiko Meguro-Horike, Yumiko Nishikawa, Hiroshi Kiyonari, Kentaro Maemura, Yuchio Yanagawa, Kunihiko Obata, Satoru Takahashi, Tomokatsu Ikawa, Rumi Satoh, Hiroshi Kawamoto, Yasuhiro Mouri and Mitsuru Matsumoto : Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-tolerance., The Journal of Experimental Medicine, Vol.205, No.12, 2827-2838, 2008. (要約) The roles of autoimmune regulator (Aire) in the expression of the diverse arrays of tissue-restricted antigen (TRA) genes from thymic epithelial cells in the medulla (medullary thymic epithelial cells [mTECs]) and in organization of the thymic microenvironment are enigmatic. We approached this issue by creating a mouse strain in which the coding sequence of green fluorescent protein (GFP) was inserted into the Aire locus in a manner allowing concomitant disruption of functional Aire protein expression. We found that Aire(+) (i.e., GFP(+)) mTECs were the major cell types responsible for the expression of Aire-dependent TRA genes such as insulin 2 and salivary protein 1, whereas Aire-independent TRA genes such as C-reactive protein and glutamate decarboxylase 67 were expressed from both Aire(+) and Aire(-) mTECs. Remarkably, absence of Aire from mTECs caused morphological changes together with altered distribution of mTECs committed to Aire expression. Furthermore, we found that the numbers of mTECs that express involucrin, a marker for terminal epidermal differentiation, were reduced in Aire-deficient mouse thymus, which was associated with nearly an absence of Hassall's corpuscle-like structures in the medulla. Our results suggest that Aire controls the differentiation program of mTECs, thereby organizing the global mTEC integrity that enables TRA expression from terminally differentiated mTECs in the thymic microenvironment. (キーワード) Animals / 細胞分化 (cell differentiation) / Cell Shape / Epithelial Cells / Female / Gene Targeting / Glutamate Decarboxylase / Green Fluorescent Proteins / Male / Mice / Mice, Inbred C57BL / Mice, Inbred Strains / Mice, Transgenic / Phenotype / Protein Precursors / Recombinant Fusion Proteins / Self Tolerance / Thymus Gland / Transcription Factors (出版サイトへのリンク) ● Publication site (DOI): 10.1084/jem.20080046 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19015306 ● Search Scopus @ Elsevier (PMID): 19015306 ● Search Scopus @ Elsevier (DOI): 10.1084/jem.20080046 (DOI: 10.1084/jem.20080046, PubMed: 19015306)
20.	Shino Niki, Kiyotaka Oshikawa, Yasuhiro Mouri, Fumiko Hirota, Akemi Matsushima, Masashi Yano, Hongwei Han, Yoshimi Bando, Keisuke Izumi, Masaki Matsumoto, Keiichi I. Nakayama, Noriyuki Kuroda and Mitsuru Matsumoto : Alteration of intra-pancreatic target-organ specificity by abrogation of Aire in NOD mice, The Journal of Clinical Investigation, Vol.116, No.5, 1292-1301, 2006. (要約) Factors that determine the spectrum of target organs involved in autoimmune destruction are poorly understood. Although loss of function of autoimmune regulator (AIRE) in thymic epithelial cells is responsible for autoimmunity, the pathogenic roles of AIRE in regulating target-organ specificity remain elusive. In order to gain insight into this issue, we have established NOD mice, an animal model of type 1 diabetes caused by autoimmune attack against beta cell islets, in which Aire has been abrogated. Remarkably, acinar cells rather than beta cell islets were the major targets of autoimmune destruction in Aire-deficient NOD mice, and this alteration of intra-pancreatic target-organ specificity was associated with production of autoantibody against pancreas-specific protein disulfide isomerase (PDIp), an antigen expressed predominantly by acinar cells. Consistent with this pathological change, the animals were resistant to the development of diabetes. The results suggest that Aire not only is critical for the control of self-tolerance but is also a strong modifier of target-organ specificity through regulation of T cell repertoire diversification. We also demonstrated that transcriptional expression of PDIp was retained in the Aire-deficient NOD thymus, further supporting the concept that Aire may regulate the survival of autoreactive T cells beyond transcriptional control of self-protein expression in the thymus. (キーワード) Animals / Autoimmune Diseases / Diabetes Mellitus / Disease Models, Animal / Female / Genetic Predisposition to Disease / Male / Mice / Mice, Inbred NOD / Mice, Transgenic / Pancreas / T-Lymphocytes / Thymus Gland / Transcription Factors (出版サイトへのリンク) ● Publication site (DOI): 10.1172/JCI26971 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16628255 ● Search Scopus @ Elsevier (PMID): 16628255 ● Search Scopus @ Elsevier (DOI): 10.1172/JCI26971 (DOI: 10.1172/JCI26971, PubMed: 16628255)
21.	Dan Kinoshita, Fumiko Hirota, Tsuneyasu Kaisho, Michiyuki Kasai, Keisuke Izumi, Yoshimi Bando, Yasuhiro Mouri, Akemi Matsushima, Shino Niki, Hongwei Han, Kiyotaka Oshikawa, Noriyuki Kuroda, Masahiko Maegawa, Minoru Irahara, Kiyoshi Takeda, Shizuo Akira and Mitsuru Matsumoto : Essential role of IkappaB kinase alpha in thymic organogenesis required for the establishment of self-tolerance., The Journal of Immunology, Vol.176, No.7, 3995-4002, 2006. (要約) IkappaB kinase (IKK) alpha exhibits diverse biological activities through protein kinase-dependent and -independent functions, the former mediated predominantly through a noncanonical NF-kappaB activation pathway. The in vivo function of IKKalpha, however, still remains elusive. Because a natural strain of mice with mutant NF-kappaB-inducing kinase (NIK) manifests autoimmunity as a result of disorganized thymic structure with abnormal expression of Rel proteins in the thymic stroma, we speculated that the NIK-IKKalpha axis might constitute an essential step in the thymic organogenesis that is required for the establishment of self-tolerance. An autoimmune disease phenotype was induced in athymic nude mice by grafting embryonic thymus from IKKalpha-deficient mice. The thymic microenvironment that caused autoimmunity in an IKKalpha-dependent manner was associated with defective processing of NF-kappaB2, resulting in the impaired development of thymic epithelial cells. Thus, our results demonstrate a novel function for IKKalpha in thymic organogenesis for the establishment of central tolerance that depends on its protein kinase activity in cooperation with NIK. (キーワード) Animals / Gene Expression Regulation / I-kappa B Kinase / Mice / ノックアウトマウス (knockout mice) / Mutation / NF-kappa B / Oncogene Proteins v-rel / Organogenesis / Protein-Serine-Threonine Kinases / Self Tolerance / Thymus Gland (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16547234 ● Summary page in Scopus @ Elsevier: 2-s2.0-33646055527 (PubMed: 16547234, Elsevier: Scopus)
22.	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. (要約) 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. (キーワード) 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 (出版サイトへのリンク) ● Publication site (DOI): 10.3410/f.1024264.287833 (文献検索サイトへのリンク) ● 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)
23.	Hiroko Akiyoshi, Shigetsugu Hatakeyama, Jukka Pitkanen, Yasuhiro Mouri, Vassilis Doucas, Jun Kudoh, Kyoko Tsurugaya, Daisuke Uchida, Akemi Matsushima, Kiyotaka Oshikawa, Keiichi I. Nakayama, Nobuyoshi Shimizu, Part Peterson and Mitsuru Matsumoto : Subcellular expression of autoimmune regulator is organized in a spatiotemporal manner, The Journal of Biological Chemistry, Vol.279, No.32, 33984-33991, 2004. (キーワード) CREB-BINDING-PROTEIN / NUCLEAR-MATRIX / NEGATIVE SELECTION / ZINC-FINGER / AIRE / GENE / DOMAINS / CELLS / PHD / LOCALIZATION (出版サイトへのリンク) ● Publication site (DOI): 10.1074/jbc.M400702200 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15150263 ● Search Scopus @ Elsevier (PMID): 15150263 ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.M400702200 (DOI: 10.1074/jbc.M400702200, PubMed: 15150263)

総説・解説:

1.	松本満, 西川裕美子, 毛利安宏, 松本穣, 西嶋仁 : T細胞の中枢免疫トレランスの機序, 月刊臨床免疫・アレルギー科, Vol.60, No.2, 70-77, 2013年7月. (キーワード) thymic epithelial cell / negative selection / regulatory T cell / Aire (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1521417753436677120 (CiNii: 1521417753436677120)
2.	西嶋仁, 毛利安宏, 西川裕美子, 松本満 : AIRE遺伝子を導入したHeLa細胞における細胞周期依存的なAIREタンパク質のリン酸化, 生化学, Vol.85, No.7, 600, 2013年7月.
3.	Mitsuru Matsumoto, Yumiko Nishikawa, Hitoshi Nishijima, Junko Morimoto, Minoru Matsumoto and Yasuhiro Mouri : Which model better fits the role of Aire in the establishment of self-tolerance: the transcription model or the maturation model?, Frontiers in Immunology, Vol.4, 1-4, Jul. 2013. (要約) The discovery of Aire-dependent transcriptional control of many tissue-restricted self-antigen (TRA) genes in thymic epithelial cells in the medulla (medullary thymic epithelial cells, mTECs) has raised the intriguing question of how the single Aire gene can influence the transcription of such a large number of TRA genes within mTECs. From a mechanistic viewpoint, there are two possible models to explain the function of Aire in this action. In the first model, TRAs are considered to be the direct target genes of Aire's transcriptional activity. In this scenario, the lack of Aire protein within cells would result in the defective TRA gene expression, while the maturation program of mTECs would be unaffected in principle. The second model hypothesizes that Aire is necessary for the maturation program of mTECs. In this case, we assume that the mTEC compartment does not mature normally in the absence of Aire. If acquisition of the properties of TRA gene expression depends on the maturation status of mTECs, a defect of such an Aire-dependent maturation program in Aire-deficient mTECs can also result in impaired TRA gene expression. In this brief review, we will focus on these two contrasting models for the roles of Aire in controlling the expression of TRAs within mTECs. (出版サイトへのリンク) ● Publication site (DOI): 10.3389/fimmu.2013.00210 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23885257 ● Summary page in Scopus @ Elsevier: 2-s2.0-84883679216 (DOI: 10.3389/fimmu.2013.00210, PubMed: 23885257, Elsevier: Scopus)

国際会議:

1.	Yasuhiro Mouri : Inter-tumor heterogeneity based on EMT state in HNSCC, International Conference on Craniofacial Pathology & Biology, Oct. 2022.
2.	Hitoshi Nishijima, Yasuhiro Mouri, Junko Morimoto and Mitsuru Matsumoto : Paradoxical development of polymyositis-like autoimmunity through augmented expression of AIRE, 7th International Workshop of Kyoto T Cell Conference, Kyoto, Japan, Mar. 2017.
3.	Hitoshi Nishijima, Yasuhiro Mouri, Junko Morimoto and Mitsuru Matsumoto : Paradoxical development of polymyositis-like autoimmunity through augmented expression of human AIRE in mice, Controversies in Rheumatology and Autoimmunity 2017, Bologna, Italy, Mar. 2017.
4.	Hiroshi Kawano, Hitoshi Nishijima, Junko Morimoto, Yasuhiro Mouri and Mitsuru Matsumoto : Aire expression is inherent to all medullary thymic epithelial cells during their differentiation program, The 4th European Congress of Immunology, Vienna, Austria, Sep. 2015.
5.	Mitsuru Matsumoto, Hiroshi Kawano, Hitoshi Nishijima, Junko Morimoto, Yasuhiro Mouri and Yasuhiko Nishioka : Aire expression is inherent properties of all medullary thymic epithelial cells during their differentiation program, Venice Thymus Meeting 2015, Venice, Italy, Apr. 2015.
6.	Hitoshi Nishijima, Junko Morimoto, Hiroshi Kawano, Yasuhiro Mouri, Koichi Ikuta and Mitsuru Matsumoto : Ectopic Aire expression in thymic cortex reveals inherent properties of Aire as a stromal factor for medullary thymic microenvironment, ThymOz 7, Heron Island, Australia, Apr. 2014.
7.	Mitsuru Matsumoto, Junko Morimoto, Hiroshi Kawano, Yasuhiro Mouri and Hitoshi Nishijima : Ectopic Aire expression in thymic cortex reveals inherent properties of Aire as a stromal factor for medullary microenvironment, 9th International Congress on Autoimmunity, Nice, France, Mar. 2014.
8.	Hitoshi Nishijima, Junko Morimoto, Yasuhiro Mouri, Yumiko Nishikawa, Kouichi Ikuta and Mitsuru Matsumoto : Ectopic Aire expression in thymic cortex reveals inherent properties of Aire as a stromal factor within medullary microenvironment, 第3回眉山免疫シンポジウム, Tokushima, Feb. 2014.
9.	Mitsuru Matsumoto, Yumiko Nishikawa, Yasuhiro Mouri and Hitoshi Nishijima : Temporal lineage tracing of Aire-expressing cells reveals a requirement of Aire for their maturation program, 15th ICI2013, Milan, Italy, Aug. 2013.
10.	Mitsuru Matsumoto, Yumiko Nishikawa, Hitoshi Nishijima, Minoru Matsumoto, Fumiko Hirota, Satoru Takahashi, Hervé Luche, Hans Fehling Joerg and Yasuhiro Mouri : Temporal lineage tracing of Aire-expressing cells reveals a requirement for Aire in their maturation program, The 6th International Workshop of Kyoto T Cell Conference, Kyoto, Japan, Jun. 2013.
11.	Mitsuru Matsumoto, Yumiko Nishikawa, Yasuhiro Mouri and Hitoshi Nishijima : Temporal fate-mapping study reveals essential roles of Aire in the maturation program of Aire-expressing cell lineage, Immunology 2013 - AAI Annual Meeting, Honolulu, Hawaii, May 2013.
12.	Yumiko Nishikawa, Yasuhiro Mouri, Hitoshi Nishijima and Mitsuru Matsumoto : Temporal lineage tracing of Aire-expressing cells reveals a requirement of Aire for their full maturation program, Controversies in Rheumatology and Autoimmunity (CORA 2011), Budapest, Hungary, Apr. 2013.
13.	Mitsuru Matsumoto, Yumiko Nishikawa, Yasuhiro Mouri and Hitoshi Nishijima : Essential roles of Aire in the maturation program of Aire-expressing cell lineage(s) revealed by temporal fate-mapping approach, The 10th International Conference on New Trends in Immunosuppression and Immunotherapy, Barcelona, Spain, Mar. 2013.
14.	Mitsuru Matsumoto, Yumiko Nishikawa, Yasuhiro Mouri, Fumiko Hirota and Hitoshi Nishijima : Temporal fate-mapping reveals essential roles of Aire in the maturation program of mTECs, ThymUS 2012, Florida, USA, Nov. 2012.
15.	Mitsuru Matsumoto, Yumiko Nishikawa, Yasuhiro Mouri and Hitoshi Nishijima : Functional analysis of Aire, a gene responsible for the hereditary type of autoimmune disease, Days of Molecular Medicine 2012, Wien, Austria, Oct. 2012.
16.	Mitsuru Matsumoto, Yumiko Nishikawa, Yasuhiro Mouri and Hitoshi Nishijima : Aire controls organization of thymic microenvironment for the establishment of self tolerance, European Congress of Immunology 2012, Glasgow, Scotland, Sep. 2012.
17.	Yasuhiro Mouri, Yumiko Nishikawa, Hitoshi Nishijima and Mitsuru Matsumoto : AIRE-dependent organization of thymic microenvironment for the establishment of self tolerance, 5th Congress of the Federation of Immunological Societies of Asia Oceania, New Delhi, India, Mar. 2012.
18.	Hitoshi Nishijima, Yasuhiro Mouri, Yumiko Nishikawa and Mitsuru Matsumoto : Cell-cycle dependent phosphorylation of AIRE protein exogenously expressed in HeLa cells, 4th International Conference on Drug Discovery & Therapy, Dubai, UAE, Feb. 2012.
19.	Mitsuru Matsumoto, Yumiko Nishikawa, Yasuhiro Mouri and Hitoshi Nishijima : Expression of Aire, a gene responsible for autoimmune disease, in ES cells, Cell Symposia: Stem Cell Programming & Re-programming, Lisbon, Portugal, Dec. 2011.
20.	Mitsuru Matsumoto, Yasuhiro Mouri, Yumiko Nishikawa and Hitoshi Nishijima : Aire-dependent organization of thymic microenvironment for the establishment of self tolerance, 5th Asian Congress on Autoimmunity, Suntec City, Singapore, Nov. 2011.
21.	Mitsuru Matsumoto, Yasuhiro Mouri, Yumiko Nishikawa and Hitoshi Nishijima : Role of self-antigen expressed by Aire-expressing cells in the negative selection process, 5th International Conference on Autoimmunity: Mechanisms and Novel Treatments, Hersonissos, Crete, Greece, Sep. 2011.
22.	Mitsuru Matsumoto, Yumiko Nishikawa, Yasuhiro Mouri and Hitoshi Nishijima : Aire-dependent organization of thymic microenvironment for the establishment of self tolerance, EUThyme-Rolduc Meeting, Leeuwenhorst, The Netherlands, May 2011.
23.	Yasuhiro Mouri, Masashi Yano, Miho Shinzawa, Yusuke Shimo, Yumiko Nishikawa, Koji Tamada, Lieping Chen, Josef M. Penninger, Jun-ichiro Inoue, Taishin Akiyama and Mitsuru Matsumoto : Lymphotoxin signal promotes thymic organogenesis by eliciting RANK expression in the embryonic thymic stroma, 13th International TNF Conference, TNF 2011, Awaji, Hyogo, May 2011.
24.	Mitsuru Matsumoto, Yumiko Nishikawa, Hitoshi Nishijima and Yasuhiro Mouri : Role of Aire in the organization of thymic microenvironment, Controversies in Rheumatology and Autoimmunity (CORA 2011), Florence, Italy, Mar. 2011.
25.	Yumiko Nishikawa, Yasuhiro Mouri, Hitoshi Nishijima and Mitsuru Matsumoto : Aire-dependent organization of thymic microenvironment for the establishment of self-tolerance, Cutting Edge Immunology and its Clinical Application, Hulshort, The Netherlands, Mar. 2011.
26.	Yasuhiro Mouri, Yumiko Nishikawa and Mitsuru Matsumoto : Aire in thymic epithelial cells in the medulla controls developmental process of thymocytes, 14th International Congress of Immunology, Kobe, Aug. 2010.
27.	Yumiko Nishikawa, Yasuhiro Mouri and Mitsuru Matsumoto : Biphasic Aire expression in early embryos and in medullary thymic epithelial cells prior to end-stage terminal differentiation, 14th International Congress of Immunology, Kobe, Aug. 2010.
28.	Yasuhiro Mouri and Mitsuru Matsumoto : Aire in thymic epithelial cells in the medulla controls developmental process of thymocytes, 7th International Congress on Autoimmunity, Ljubljana, Slovenia, May 2010.
29.	Mitsuru Matsumoto, Yumiko Nishikawa, Fumiko Hirota and Yasuhiro Mouri : AIRE and autoimmune disease, The 19th International Rheumatology Symposium, Kobe, Apr. 2010.
30.	Mitsuru Matsumoto, Yumiko Nishikawa, Fumiko Hirota, Masashi Yano, Hiroshi Kawamoto and Yasuhiro Mouri : Biphasic Aire expression in early embryos and in medullary thymic epithelial cells prior to end-stage terminal differentiation, ThymOz VI, Gladstone, Australia, Mar. 2010.
31.	Mitsuru Matsumoto, Yumiko Nishikawa, Masashi Yano, Fumiko Hirota and Yasuhiro Mouri : Aire-dependent organization of thymic microenvironment, International KTCC 2009, Kyoto, Jun. 2009.
32.	Yasuhiro Mouri, Masashi Yano and Mitsuru Matsumoto : Roles of NIK in thymic epithelial cells for the establishment of central tolerance., 12th International TNF Conference, Madrid, Apr. 2009.

国内講演発表:

1.	猿棒元陽, 毛利安宏, Guardavaccaro Daniele, 工藤保誠 : 腸上皮幹細胞におけるRNF32ユビキチンリガーゼの役割, 第47回日本分子生物学会年会, 2024年11月.
2.	siqi chen, Natsumi Fujiwara, Yasuhiro Mouri and Yasusei Kudo : Oral cancer microenvironment for promoting the biofilm formation of Fusobacterium nucleatum, 第83回日本癌学会学術総会, Sep. 2024.
3.	Wenhua Shao, Yasuhiro Mouri, Takeshi Oya and Yasusei Kudo : The role of Fat1 gene mutation in the development of maxillofacial anomalies, 第113回日本病理学会総会, Mar. 2024.
4.	卲文華, 毛利安宏, 尾矢剛志, 工藤保誠 : The novel function of Fat1 gene mutation in the development of maxillofacial anomalies, 第129回日本解剖学会総会・全国学術集会, 2024年3月.
5.	Jin Shengjian, 常松貴明, 堀口大吾, 毛利安宏, 卲文華, 三好圭子, 水澤典子, Hagita Hiroko, 猿棒元陽, 吉田佳世, 吉田賀弥, 藤原奈津美, 尾崎和美, 石丸直澄, 工藤保誠 : 頭頸部扁平上皮癌(HNSCC)の進行における脱ユビキチン化酵素 OTUB1 の役割, 第82回日本癌学会学術集会, 2023年9月.
6.	猿棒元陽, 諸見里昭, 山田梓紗, 卲文華, Jin Shengjian, 毛利安宏, 工藤保誠 : 頸部扁平上皮癌の partial-EMT における TGFBI の役割, 第82回日本癌学会学術総会, 2023年9月.
7.	吉田佳世, 吉田賀弥, 瀬山真莉子, 芽形真奈, 藤原奈津美, 水澤典子, 毛利安宏, 工藤保誠, 尾崎和美 : 歯周病原菌由来細胞外小胞を介した肺炎発症メカニズムの解明, 第66回春季日本歯周病学会学術大会, 2023年5月.
8.	山村佳子, 毛利安宏, 鎌田久美子, 栗尾奈愛, 工藤景子, 工藤保誠, 宮本洋二 : 唾液腺の発達・再生におけるNrepの役割, 第77回NPO法人日本口腔科学会学術集会, 2023年5月.
9.	Wenhua Shao, Yasuhiro Mouri and Yasusei Kudo : The role of Fat1 in maxillofacial development, 第112回日本病理学会総会, Apr. 2023.
10.	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.
11.	猿棒元陽, 山田梓紗, 卲文華, 金晟劍, 毛利安宏, 工藤保誠 : Transforming growth factor beta-induced (TGFBI)の役割, 第61回四国歯学会, 2023年3月.
12.	Wenhua Shao, Yasuhiro Mouri and Yasusei Kudo : The novel function of Fat1 in maxillofacial development, 第45回日本分子生物学会年会, Dec. 2022.
13.	Sarubou Motoharu, 卲文華, 毛利安宏, 工藤保誠 : 口腔癌の進展における TGFβ1の役割, 第45回日本分子生物学会年会, 2022年12月.
14.	Wenhua Shao, Yasuhiro Mouri and Yasusei Kudo : The novel function Fat1 in maxillofacial development, 第45回日本分子生物学会年会, Nov. 2022.
15.	毛利安宏, 木曽田暁, 工藤保誠 : 頭頸部扁平上皮がんの予後を予測する部分上皮間葉転換リスクモデルの構築, 第64回歯科基礎医学会学術大会, 2022年9月.
16.	Wenhua Shao, Yasuhiro Mouri and Yasusei Kudo : 額顔面形成におけるFat1の役割, 第64回歯科基礎医学会学術大会, Sep. 2022.
17.	大本美奈, 寺島実遥, 三宅夏穂, 森内快郁, 卲文華, 毛利安宏, 工藤保誠 : 阻害剤スクリーニングによる多能性制御因子の同定, 第64回歯科基礎医学会学術大会, 2022年9月.
18.	猿棒元陽, 邵文華, 山口裕太, 毛利安宏, 工藤保誠 : 口腔癌の進展におけるTransforming growth factor beta-induced(TGFB1)の役割, 第64回歯科基礎医学会学術大会, 2022年9月.
19.	Bunka Sho, Yasuhiro Mouri and Yasusei Kudo : The role of Fat1 in maxillofacial development, 第39回分子病理学研究会, Jul. 2022.
20.	毛利安宏, 工藤保誠 : 部分上皮間葉転換に基づくHNSCCの予後予測モデルの構築, 第39回分子病理学研究会, 2022年7月.
21.	Wenhua Shao, Yasuhiro Mouri and Yasusei Kudo : The role of Fat1 gene mutation in maxillofacial dysplasia, 第111回日本病理学会総会, Apr. 2022.
22.	工藤保誠, 常松貴明, 毛利安宏 : Aurora-Bキナーゼ阻害剤による多能性幹細胞の分化誘導, 第95回日本薬理学会年会, 2022年3月.
23.	卲文華, 藤原奈津美, 毛利安宏, 工藤保誠 : フソバクテリウム・ヌクレアタム感染による上皮性からp-EMT表現型への変換は，口腔癌細胞の浸潤を促進する,, 第44回日本分子生物学会年会, 2021年12月.
24.	木曽田暁, 卲文華, 金晟劍, 毛利安宏, 工藤保誠 : クロスプラットフォーム正規化と機械学習を利用した頭頚部扁平上皮癌の予後予測モデルの構築, 第80回日本癌学会学術総会, 2021年10月.
25.	毛利安宏 : 唾液腺幹/前駆細胞の維持・分化を制御する遺伝子ネットワークの構築, 第12回RNAi研究会, 2021年8月.
26.	山村佳子, 工藤保誠, 毛利安宏, 卲文華, 横田美保, 宮本洋二 : 腺房細胞の再生に関わる遺伝子ネットワークの同定, 第75回日本口腔科学会学術集会, 2021年5月.
27.	Hitoshi Nishijima, Yoshiki Matsuoka, Yasuhiro Mouri, Junko Morimoto and Mitsuru Matsumoto : Possible defect in the Treg production in mice overexpressing AIRE/Aire which exhibit muscle-specific autoimmunity, 第45回日本免疫学会学術集会, Dec. 2016.
28.	Junko Morimoto, Yumiko Nishikawa, Hiroshi Kawano, Yasuhiro Mouri, Hitoshi Nishijima and Mitsuru Matsumoto : A novel Aire-dependent subset of medullary thymic epithelial cells that express Ly6 family protein, 第44回日本免疫学会学術集会, Nov. 2015.
29.	Hitoshi Nishijima, Yasuhiro Mouri, Junko Morimoto, Hiroshi Kawano and Mitsuru Matsumoto : Paradoxical development of polymyositis-like autoimmunity by the additive expression of AIRE, 第44回日本免疫学会学術集会, Nov. 2015.
30.	Hitoshi Nishijima, Junko Morimoto, Yasuhiro Mouri, Hiroshi Kawano, Koichi Ikuta and Mitsuru Matsumoto : Approaches to identify Aire-regulated non-tissue-restricted antigen genes by the ectopic expression of Aire in thymic cortex, 第43回日本免疫学会学術集会, Dec. 2014.
31.	Hiroshi Kawano, Junko Morimoto, Yasuhiro Mouri, Hitoshi Nishijima, Yasuhiko Nishioka and Mitsuru Matsumoto : Unexpected disturbance of the development of medullary thymic epithelial cells at immature stages by the long-term ablation of mature Aire-expressing cells, 第43回日本免疫学会学術集会, Dec. 2014.
32.	Hitoshi Nishijima, Junko Morimoto, Yasuhiro Mouri, Yumiko Nishikawa, Kouichi Ikuta and Mitsuru Matsumoto : Requirement of Aire expression within thymic medulla but not cortex for establishing self-tolerance, 第42回日本免疫学会総会, Dec. 2013.
33.	西嶋仁, 毛利安宏, 西川裕美子, 松本満 : AIRE遺伝子を導入したHeLa細胞における細胞周期依存的なAIREタンパク質のリン酸化, 第35回日本分子生物学会年会, 2012年12月.
34.	毛利安宏, 西川裕美子, 西嶋仁, 松本満 : 2つのトランスジェニックモデルにおける負の選択機構におけるAire依存性の相違, 第41回日本免疫学会学術集会, 2012年12月.

その他・研究会:

1.	毛利安宏 : 口腔エコシステム構築機構の解明, 四国歯学会第59回例会, 2022年3月.
2.	西嶋仁, 松岡慶樹, 毛利安宏, 森本純子, 松本満 : ヒトAIRE トランスジェニックマウスに誘導される多発性筋炎病態の解析, 第36回日本胸腺研究会, 2017年2月.
3.	西嶋仁, 梶本達也, 松岡慶樹, 毛利安宏, 森本純子, 河野弘, 松本満 : NOD系統特異的に多発性筋炎様症状をもたらすゲノム領域の解析, 第14回四国免疫フォーラム, 2015年6月.
4.	西嶋仁, 毛利安宏, 西川裕美子, 松本満 : AIRE遺伝子を導入したHeLa細胞における細胞周期依存的なAIREタンパク質のリン酸化, 第54回日本生化学会中国・四国支部例会, 2013年5月.

科学研究費補助金 (KAKEN Grants Database @ NII.ac.jp)

歯周病が惹起する全身炎症性疾患の機序解明と酸化ストレス制御による予防法確立 (研究課題/領域番号: 23K09333 )
FAT1遺伝子変異がもたらす顎顔面形成不全分子メカニズムの解明 (研究課題/領域番号: 22K19629 )
遺伝的多様性に基づいた新規口腔がん特異的分子標的の探索 (研究課題/領域番号: 23K24546 )
Fusobacterium nucleatum感染による口腔癌病態の解明 (研究課題/領域番号: 22K10342 )
唾液腺幹/前駆細胞の維持・再生に関わる遺伝子の同定と新たな口腔乾燥症治療への応用 (研究課題/領域番号: 22K10121 )
口腔がんにおける免疫環境構築機構の解明 (研究課題/領域番号: 22K09926 )
RNA修飾による糖脂質分解酵素活性制御機構の解明とゴーシェ病克服への挑戦 (研究課題/領域番号: 22K09913 )
口腔がん幹細胞に対する新規分子標的探索とその応用による口腔がん治療戦略基盤の確立 (研究課題/領域番号: 21KK0162 )
Aireによる胸腺内抗原提示細胞の機能制御の解析 (研究課題/領域番号: 16K08840 )
AIREの機能解析による自己免疫病態の解明 (研究課題/領域番号: 16H05342 )
胸腺髄質上皮細胞による負の選択制御機構の解析 (研究課題/領域番号: 25860363 )
根本的治療法確立のための遺伝性自己免疫疾患の病態解明 (研究課題/領域番号: 25293223 )
難治性皮膚疾患・乾癬の免疫病態解析 (研究課題/領域番号: 22791078 )
疾患モデルマウスを用いた遺伝性自己免疫疾患の病態解析 (研究課題/領域番号: 21390298 )
研究者番号（80464353）による検索

講師 : 毛利安宏

研究活動

個人のホームページ

専門分野

研究テーマ

著書・論文

学術論文(審査論文):

総説・解説:

国際会議:

国内講演発表:

その他・研究会:

科学研究費補助金 (KAKEN Grants Database @ NII.ac.jp)

講師 : 毛利 安宏

研究活動

個人のホームページ

専門分野

研究テーマ

著書・論文

学術論文(審査論文):

総説・解説:

国際会議:

国内講演発表:

その他・研究会:

科学研究費補助金 (KAKEN Grants Database @ NII.ac.jp)

講師 : 毛利安宏