mouri/published_papers/54435280 Zichao Lu, Yasuhiro Mouri, Wenhua Shao, Akihiro Yasue, Chunhua Wang, Hiroko Hagita, Kiyotake Yamamoto, Naoko Matsumoto, Minoru Matsumoto, Takeshi Oya, Yasusei Kudo Imbalanced p53–RB signaling triggers cGAS–STING–mediated immune activation in early oral cancer development Oncogene 45 4303 4316 20260800 mouri/published_papers/53007054 Soichiro Kinjo Yasuhiro Mouri Wenhua Shao Satoshi Fukumoto Eiji Tanaka Yasusei Kudo Keiko Miyoshi Spatiotemporal profiling of Fat family genes highlights Fat2 as a novel marker of outer enamel epithelium and stratum intermedium Elsevier BV Journal of Oral Biosciences 1349-0079 68 2 null null 20260400 10.1016/j.job.2026.100766 41862271 mouri/published_papers/52739325 Angela Lauriola Juliana Haydeé Enriqué Steinberg Motoharu Sarubo Elena Maspero Fabiana Alejandra Rossi Yasuhiro Mouri Marco Pedretti Mohsen Hajisadeghian Vincenzo Taibi Andrea Vettori Nicola Vitulo Michael Assfalg Mariapina D'Onofrio Mario Rossi Akihiro Yasue Alessandra Astegno Simona Polo Spartaco Santi Yasusei Kudo Daniele Guardavaccaro The E3 ligase RNF32 controls the IκB kinase complex and NF-κB signaling in intestinal stem cells Elsevier BV Molecular Cell 1097-2765 85 22 4254 4267.e9 20251100 10.1016/j.molcel.2025.10.005 41167191 mouri/published_papers/52483151 Kunihiro Otsuka Aya Ushio Ruka Nagao Shigefumi Matsuzawa Rieko Arakaki Kazuki Fukuta Yasuhiro Mouri Takaaki Tsunematsu Naozumi Ishimaru Regulatory Role of FGL‐1 in Interorgan Communication by Controlling T Cell Homeostasis During the Onset of Sjögren Disease Objective Autoimmunity occurs due to the tactics between pathogenic and regulatory factors in systemic organs. Although interorgan communication has been demonstrated in various diseases, the effects of the crosstalk between the immune system and other organs on autoimmune disease is unknown. Methods We analyzed the influence of interorgan communication on the cellular or molecular mechanism of autoimmunity using a mouse model of primary Sjögren disease (pSjD) and patients with pSjD by integrative genomic, bioinformatic, pathologic, and immunologic analyses. Results Fibrinogen‐like protein‐1 (FGL‐1) was identified as a potent factor for interorgan communication between the liver and immune system in pSjD model mice. The production of FGL‐1 of the liver is induced by interleukin‐6 (IL‐6) from CD4 ⁺ T cells in these mice. The onset of autoimmune lesions in an Fgl1 ‐deficient pSjD model mice was earlier than that in the wild type pSjD model mice. FGL‐1 produced in the liver regulates naïve and memory T cell homeostasis. Further, FGL‐1 was significantly up‐regulated in patients with pSjD compared to the controls. Moreover, its concentration was closely related to the serum IL‐6 levels in patients with pSjD. Conclusion FGL‐1 plays a key role in the onset of autoimmunity by suppressing T cell activation in pSjD. Our results will facilitate the development of novel diagnostic or therapeutic strategies targeting the interorgan communication for autoimmune diseases. image Wiley Arthritis & Rheumatology 2326-5205 77 11 1573 1584 20251100 10.1002/art.43236 40395191 mouri/published_papers/47811636 Kumiko Kamada Naito Kurio Yasuhiro Mouri Yasusei Kudo Combination treatment with hyaluronic acid synthesis and Bcl-2 inhibitors induces senolytic elimination of oral squamous cell carcinoma cells in vitro Elsevier BV Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 2212-5558 37 289 296 20250300 10.1016/j.ajoms.2024.09.003 mouri/published_papers/49948355 Takaaki Tsunematsu Yasuhiro Mouri Wenhua Shao Rieko Arakaki Jan G. Ruppert Kensaku Murano Naozumi Ishimaru Daniele Guardavaccaro Michele Pagano Yasusei Kudo Sustained chromosomal passenger complex activity preserves the pluripotency of human embryonic carcinoma cells Human embryonic carcinoma (hEC) cells are derived from teratocarcinomas, exhibit robust proliferation, have a high differentiation potential, are the malignant counterparts of human embryonic stem cells (hESCs), and are considered hESC-like. The chromosomal passenger complex (CPC), made up of the microtuble binding protein Borealin, the kinase Aurora-B, the CPC-stabilizing inner centromere protein (INCENP), and the inhibitor of apoptosis family member Survivin, regulates cell division and is active exclusively during mitosis in somatic cells. The anaphase-promoting complex/cyclosome and its cofactor Cdh1 (APC/C ^Cdh1 ) is a ubiquitylating complex that catalyzes the degradation of Aurora-B and Borealin in somatic cells but has low activity during interphase in hESCs. Here, we found that Borealin and Aurora-B exhibited sustained stability throughout the cell cycle of hEC cells due to low APC/C ^Cdh1 activity. In contrast with somatic cells, CPC activity persisted across the cell cycle of hEC cells because of diminished APC/C ^Cdh1 activity. Disrupting the CPC complex by depleting its constituents triggered spontaneous differentiation in hEC cells. As hEC cells differentiated, APC/C ^Cdh1 activation curtailed CPC activity. Inactivating the CPC by pharmacologically inhibiting Aurora-B induced hEC cell differentiation by activating the epithelial-to-mesenchymal transition (EMT) program. Hence, APC/C ^Cdh1 -mediated termination of CPC activity triggered hEC cell differentiation. Collectively, these findings demonstrate a role for the CPC in governing hESC cell fate. American Association for the Advancement of Science (AAAS) Science Signaling 1937-9145 18 874 null null 20250200 10.1126/scisignal.adg4626 40136047 mouri/published_papers/52763222 Noboru Hashimoto Shizuka Ito Akira Harazono Akiko Tsuchida Yasuhiro Mouri Akihito Yamamoto Tetsuya Okajima Yuhsuke Ohmi Keiko Furukawa Yasusei Kudo Nana Kawasaki Koichi Furukawa Bidirectional signals generated by Siglec-7 and its crucial ligand tri-sialylated T to escape of cancer cells from immune surveillance iScience 2589-0042 27 11 null null 20241000 10.1016/j.isci.2024.111139 mouri/published_papers/53007201 Kayo Yoshida Kaya Yoshida Yasuhiro Mouri Ayu Takai Mariko Seyama Mana Mekata Noriko Mizusawa Keiko Miyoshi Yasusei Kudo Kazumi Ozaki Porphyromonas gingivalis infection alters microRNA composition in extracellular vesicles Elsevier BV Journal of Oral Biosciences 1349-0079 66 2 365 372 20240600 10.1016/j.job.2024.04.001 38579987 mouri/published_papers/52665762 Motoharu Sarubo Yasuhiro Mouri Akira Moromizato Azusa Yamada Shengjan Jin Wenhua Shao Hiroko Hagita Keiko Miyoshi Yasusei Kudo Involvement of TGFBI-TAGLN axis in cancer stem cell property of head and neck squamous cell carcinoma Abstract 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. Springer Science and Business Media LLC Scientific Reports 2045-2322 14 1 null null 20240300 10.1038/s41598-024-57478-0 38514830 mouri/published_papers/44134718 Shengjian Jin Takaaki Tsunematsu Taigo Horiguchi Yasuhiro Mouri Wenhua Shao Keiko Miyoshi Hiroko Hagita Motoharu Sarubo Natsumi Fujiwara Guangying Qi Naozumi Ishimaru Yasusei Kudo Involvement of the OTUB1‐YAP1 axis in driving malignant behaviors of head and neck squamous cell carcinoma Abstract Background Comprehending the molecular mechanisms underlying head and neck squamous cell carcinoma (HNSCC) is vital for the development of effective treatment strategies. Deubiquitinating enzymes (DUBs), which regulate ubiquitin‐dependent pathways, are potential targets for cancer therapy because of their structural advantages. Here we aimed to identify a potential target for HNSCC treatment among DUBs. Methods A screening process was conducted using RNA sequencing data and clinical information from HNSCC patients in the TCGA database. A panel of 88 DUBs was analyzed to identify those associated with poor prognosis. Subsequently, HNSCC cells were modified to overexpress specific DUBs, and their effects on cell proliferation and invasion were evaluated. In vivo experiments were performed to validate the findings. Results 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. Conclusions 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. Wiley Cancer Medicine 2045-7634 12 24 22156 22169 20231200 10.1002/cam4.6735 37986681 mouri/published_papers/41269741 Shao Wenhua Takaaki Tsunematsu Masaaki Umeda Hiroaki Tawara Natsumi Fujiwara Yasuhiro Mouri Rieko Arakaki Naozumi Ishimaru Yasusei Kudo Cancer cell-derived novel periostin isoform promotes invasion in head and neck squamous cell carcinoma 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. Cancer Medicine 12 7 8510 8525 20230400 10.1002/cam4.5601 36691359 mouri/published_papers/42744618 Yoshiko Yamamura Keiko Miyoshi Yasuhiro Mouri Yasusei Kudo Youji Miyamoto miR-155-5p can be involved in acquisition of osseointegration on titanium surface Springer Science and Business Media LLC In Vitro Cellular & Developmental Biology - Animal 1543-706X 58 8 693 701 20220900 10.1007/s11626-022-00718-2 mouri/published_papers/37952708 Satoru Kisoda Yasuhiro Mouri Naoya Kitamura Tetsuya Yamamoto Keiko Miyoshi Yasusei Kudo The role of partial-EMT in the progression of head and neck squamous cell carcinoma Elsevier BV Journal of Oral Biosciences 1349-0079 64 2 176 182 20220600 10.1016/j.job.2022.02.004 35176487 mouri/published_papers/34931344 Wenhua Shao Natsumi Fujiwara Yasuhiro Mouri Satoru Kisoda Kayo Yoshida Kaya Yoshida Hiromichi Yumoto Kazumi Ozaki Naozumi Ishimaru Yasusei Kudo Conversion from epithelial to partial-EMT phenotype by Fusobacterium nucleatum infection promotes invasion of oral cancer cells <title>Abstract</title> The ability of cancer cells to undergo partial-epithelial mesenchymal transition (p-EMT), rather than complete EMT, poses a higher metastatic risk. Although <italic>Fusobacterium nucleatum</italic> mainly inhabits in oral cavity, attention has been focused on the <italic>F. nucleatum</italic> involvement in colorectal cancer development. Here we examined the p-EMT regulation by <italic>F. nucleatum</italic> in oral squamous cell carcinoma (OSCC) cells. We cultured OSCC cells with epithelial, p-EMT or EMT phenotype with live or heat-inactivated <italic>F. nucleatum</italic>. Expression of the genes involved in epithelial differentiation, p-EMT and EMT were examined in OSCC cells after co-culture with <italic>F. nucleatum</italic> by qPCR. Cell growth and invasion of OSCC cells were also examined. Both live and heat-inactivated <italic>F. nucleatum</italic> upregulated the expression of p-EMT-related genes in OSCC cells with epithelial phenotype, but not with p-EMT or EMT phenotype. Moreover, <italic>F. nucleatum</italic> promoted invasion of OSCC cells with epithelial phenotype. Co-culture with other strains of bacteria other than <italic>Porphyromonas gingivalis</italic> did not alter p-EMT-related genes in OSCC cells with epithelial phenotype. <italic>F. nucleatum</italic> infection may convert epithelial to p-EMT phenotype via altering gene expression in OSCC. Oral hygiene managements against <italic>F. nucleatum</italic> infection may contribute to reduce the risk for an increase in metastatic ability of OSCC. Springer Science and Business Media LLC Scientific Reports 2045-2322 11 1 null null 20210700 10.1038/s41598-021-94384-1 mouri/published_papers/34919495 Go Ohe Yasusei Kudo Kumiko Kamada Yasuhiro Mouri Natsumi Takamaru Keiko Kudoh Naito Kurio Youji Miyamoto The Soluble Factor from Oral Cancer Cell Lines Inhibits Interferon-γ Production by OK-432 via the CD40/CD40 Ligand Pathway (1) Background: OK-432 is a penicillin-killed, lyophilized formulation of a low-toxicity strain (Su) of Streptococcus pyogenes (Group A). It is a potent immunotherapy agent for several types of cancer, including oral cancer. We previously showed that (i) OK-432 treatment induces a high amount of IFN-γ production from peripheral blood mononuclear cells (PBMCs), and (ii) conditioned medium (CM) from oral cancer cells suppresses both the IFN-γ production and cytotoxic activity of PBMCs driven by OK-432. The aim of this study was to determine the inhibitory mechanism of OK-432-induced IFN-γ production from PBMCs by CM. (2) Methods: We performed cDNA microarray analysis, quantitative RT-PCR, and ELISA to reveal the inhibitory mechanism of CM. (3) Results: We found that CD40 plays a key role in IFN-γ production via IL-12 production. Although OK-432 treatment upregulated the expression levels of the IL-12p40, p35, and CD40 genes, CM from oral cancer cells downregulate these genes. The amount of IFN-γ production by OK-432 treatment was decreased by an anti-CD40 neutralizing antibody. (4) Conclusions: Our study suggests that uncertain soluble factor(s) produced from oral cancer cells may inhibit IFN-γ production from PBMCs via suppressing the CD40/CD40L–IL-12 axis. MDPI AG Cancers 2072-6694 13 13 null null 20210600 10.3390/cancers13133301 34209347 mouri/published_papers/26408739 Satoru Kisoda Wenhua Shao Natsumi Fujiwara Yasuhiro Mouri Takaaki Tsunematsu Shengjian Jin Rieko Arakaki Naozumi Ishimaru Yasusei Kudo Prognostic value of partial EMT‐related genes in head and neck squamous cell carcinoma by a bioinformatic analysis Abstract Objective Recent studies have revealed that the ability of cancer cells to undergo intermediate state of epithelial‐to‐mesenchymal transition (EMT), partial EMT (p‐EMT), poses a higher metastatic risk rather than complete EMT. Here, we examined the prognostic value of p‐EMT‐related genes in head and neck squamous cell carcinoma (HNSCC) by bioinformatic approaches. Materials and methods We used RNA‐seq data of 519 primary HNSCC cases obtained from TCGA database. We compared the expression of p‐EMT‐related genes in HNSCC tissues with normal tissues. We evaluated the prognostic value of p‐EMT‐related genes in HNSCC cases by log‐rank test. We examined the expression of p‐EMT‐, EMT‐, and epithelial differentiation‐related genes by qPCR. Results Among p‐EMT‐related genes that were highly expressed in HNSCC cases, high expression of SERPINE1, ITGA5, TGFBI, P4HA2, CDH13, and LAMC2 was significantly correlated with poor survival of HNSCC patients. By gene expression pattern, HNSCC cell lines were classified into three groups: epithelial phenotype, EMT phenotype, and p‐EMT phenotype. Conclusions 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. Wiley Oral Diseases 1601-0825 26 6 1149 1156 20200900 10.1111/odi.13351 32277532 mouri/published_papers/221005 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 Mitsuru Matsumoto Paradoxical development of polymyositis-like autoimmunity through augmented expression of autoimmune regulator (AIRE) Elsevier BV Journal of Autoimmunity 0896-8411 86 75 92 20180100 10.1016/j.jaut.2017.09.006 28931462 mouri/published_papers/221004 Yasuhiro Mouri Yoshihiro Ueda Tomoyoshi Yamano Minoru Matsumoto Koichi Tsuneyama Tatsuo Kinashi 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 1550-6606 199 12 3959 3971 20171200 10.4049/jimmunol.1700892 29101311 mouri/published_papers/221006 Hiroshi Kawano Hitoshi Nishijima Junko Morimoto Fumiko Hirota Ryoko Morita Yasuhiro Mouri Yasuhiko Nishioka Mitsuru Matsumoto Aire Expression Is Inherent to Most Medullary Thymic Epithelial Cells during Their Differentiation Program Abstract 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 &amp;gt;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. Oxford University Press (OUP) The Journal of Immunology 1550-6606 195 11 5149 5158 20151200 10.4049/jimmunol.1501000 26503950 mouri/published_papers/221007 Hitoshi Nishijima Satsuki Kitano Hitoshi Miyachi Junko Morimoto Hiroshi Kawano Fumiko Hirota Ryoko Morita Yasuhiro Mouri Kiyoshi Masuda Issei Imoto Koichi Ikuta Mitsuru Matsumoto Ectopic Aire Expression in the Thymic Cortex Reveals Inherent Properties of Aire as a Tolerogenic Factor within the Medulla Abstract 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. Oxford University Press (OUP) The Journal of Immunology 1550-6606 195 10 4641 4649 20151100 10.4049/jimmunol.1501026 26453754 mouri/published_papers/221008 Yasuhiro Mouri Hitoshi Nishijima Hiroshi Kawano Fumiko Hirota Nobuo Sakaguchi Junko Morimoto 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 1550-6606 193 9 4356 4367 20141100 10.4049/jimmunol.1400389 25261487 mouri/published_papers/221009 Yumiko Nishikawa Hitoshi Nishijima Minoru Matsumoto Junko Morimoto Fumiko Hirota Satoru Takahashi Hervé Luche Hans Joerg Fehling Yasuhiro Mouri Mitsuru Matsumoto Temporal Lineage Tracing of Aire-Expressing Cells Reveals a Requirement for Aire in Their Maturation Program The Journal of Immunology 1550-6606 192 6 2585 2592 20140300 10.4049/jimmunol.1302786 24516201 mouri/published_papers/25105232 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 Toshio Matsumoto Androgen Receptor Promotes Sex-Independent Angiogenesis in Response to Ischemia and Is Required for Activation of Vascular Endothelial Growth Factor Receptor Signaling Background— Hypoandrogenemia is associated with an increased risk of ischemic diseases. Because actions of androgens are exerted through androgen receptor (AR) activation, we studied hind-limb ischemia in AR knockout mice to elucidate the role of AR in response to ischemia. Methods and Results— Both male and female AR knockout mice exhibited impaired blood flow recovery, more cellular apoptosis, and a higher incidence of autoamputation after ischemia. In ex vivo and in vivo angiogenesis studies, AR-deficient vascular endothelial cells showed reduced angiogenic capability. In ischemic limbs of AR knockout mice, reductions in the phosphorylation of the Akt protein kinase and endothelial nitric oxide synthase were observed despite a robust increase in hypoxia-inducible factor 1α and vascular endothelial cell growth factor ( VEGF ) gene expression. In in vitro studies, siRNA-mediated ablation of AR in vascular endothelial cells blunted VEGF-stimulated phosphorylation of Akt and endothelial nitric oxide synthase. Immunoprecipitation experiments documented an association between AR and kinase insert domain protein receptor that promoted the recruitment of downstream signaling components. Conclusions— 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. Ovid Technologies (Wolters Kluwer Health) Circulation 1524-4539 128 1 60 71 20130700 10.1161/circulationaha.113.001533 23723256 mouri/published_papers/221012 Mitsuru Matsumoto Yumiko Nishikawa Hitoshi Nishijima Junko Morimoto Minoru Matsumoto Yasuhiro Mouri Which Model Better Fits the Role of Aire in the Establishment of Self-Tolerance: The Transcription Model or the Maturation Model? Frontiers Media SA Frontiers in Immunology 1664-3224 4 null null 20130700 10.3389/fimmu.2013.00210 23885257 mouri/published_papers/221011 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 Mitsuru Matsumoto Lymphotoxin Signal Promotes Thymic Organogenesis by Eliciting RANK Expression in the Embryonic Thymic Stroma The Journal of Immunology 1550-6606 186 9 5047 5057 20110500 10.4049/jimmunol.1003533 21441458 mouri/published_papers/221010 Yumiko Nishikawa Fumiko Hirota Masashi Yano Hiroyuki Kitajima Jun-ichi Miyazaki Hiroshi Kawamoto Yasuhiro Mouri Mitsuru Matsumoto Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation 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+CD80high mTECs further progressed to an Aire-CD80intermediate 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. Rockefeller University Press Journal of Experimental Medicine 1540-9538 207 5 963 971 20100500 10.1084/jem.20092144 20404099 mouri/published_papers/221014 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 Mitsuru Matsumoto Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-tolerance 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. Rockefeller University Press Journal of Experimental Medicine 1540-9538 205 12 2827 2838 20081100 10.1084/jem.20080046 19015306 mouri/published_papers/221015 Mitsuru Matsumoto Yiqing Zhou Shinji Matsuo Hideki Nakanishi Kenji Hirose Hajimu Oura Seiji Arase Akemi Ishida-Yamamoto Yoshimi Bando Keisuke Izumi Hiroshi Kiyonari Naoko Oshima Rika Nakayama Akemi Matsushima Fumiko Hirota Yasuhiro Mouri Noriyuki Kuroda Shigetoshi Sano David D. Chaplin Targeted deletion of the murine corneodesmosin gene delineates its essential role in skin and hair physiology Controlled proteolytic degradation of specialized junctional structures, corneodesmosomes, by epidermal proteases is an essential process for physiological desquamation of the skin. Corneodesmosin (CDSN) is an extracellular component of corneodesmosomes and, although considerable debate still exists, genetic studies have suggested that the CDSN gene in the major psoriasis-susceptibility locus ( PSORS1 ) may be responsible for susceptibility to psoriasis, a human skin disorder characterized by excessive growth and aberrant differentiation of keratinocytes. CDSN is also expressed in the inner root sheath of hair follicles, and a heterozygous nonsense mutation of the CDSN gene in humans is associated with scalp-specific hair loss of poorly defined etiology. Here, we have investigated the pathogenetic roles of CDSN loss of function in the development of skin diseases by generating a mouse strain with targeted deletion of the Cdsn gene. Cdsn -deficient mouse skin showed detachment of the stratum corneum from the underlying granular layer and/or detachment within the upper granular layers due to the disrupted integrity of the corneodesmosomes. When grafted onto immunodeficient mice, Cdsn -deficient skin showed rapid hair loss together with epidermal abnormalities resembling psoriasis. These results underscore the essential roles of CDSN in hair physiology and suggest functional relevance of CDSN gene polymorphisms to psoriasis susceptibility. Proceedings of the National Academy of Sciences Proceedings of the National Academy of Sciences 1091-6490 105 18 6720 6724 20080500 10.1073/pnas.0709345105 18436651 mouri/published_papers/221016 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 Mitsuru Matsumoto Alteration of intra-pancreatic target-organ specificity by abrogation of Aire in NOD mice American Society for Clinical Investigation Journal of Clinical Investigation 0021-9738 116 5 1292 1301 20060500 10.1172/jci26971 16628255 mouri/published_papers/221017 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 Mitsuru Matsumoto Essential role of IkappaB kinase alpha in thymic organogenesis required for the establishment of self-tolerance 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. The Journal of immunology 0022-1767 176 7 3995 4002 20060400 16547234 mouri/published_papers/221018 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 Mitsuru Matsumoto Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus of Aire-deficient mice 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. The Journal of Immunology 0022-1767 174 4 1862 1870 20050200 15699112 mouri/published_papers/221019 Hiroko Akiyoshi Shigetsugu Hatakeyama Jukka Pitkänen Yasuhiro Mouri Vassilis Doucas Jun Kudoh Kyoko Tsurugaya Daisuke Uchida Akemi Matsushima Kiyotaka Oshikawa Keiichi I Nakayama Nobuyoshi Shimizu Pärt Peterson Mitsuru Matsumoto Subcellular Expression of Autoimmune Regulator Is Organized in a Spatiotemporal Manner Elsevier BV Journal of Biological Chemistry 0021-9258 279 32 33984 33991 20040800 10.1074/jbc.m400702200 15150263 mouri/misc/24709681 松本 満 西川 裕美子 毛利 安宏 松本穣 西嶋仁 Mechanisms underlying the establishment of T-cell tolerance in the thymus T細胞の中枢免疫トレランスの機序 科学評論社 臨床免疫・アレルギー科 1881-1930 60 1 72 77 20130700 mouri/misc/24709682 毛利 安宏 西川 裕美子 西嶋 仁 松本満 Role of lymphotoxin for thymic organogenesis 胸腺の形成とリンホトキシン 科学評論社 臨床免疫・アレルギー科 1881-1930 58 2 234 238 20120800 mouri/misc/53030163 松本満 西嶋仁 西川裕美子 毛利安宏 先端医学講座 Aireと自己免疫疾患 月刊アレルギーの臨床 0285-6379 433 null null 20120000 mouri/misc/24709683 松本 満 西川 裕美子 毛利 安宏 新居卓朗 西嶋仁 Role of AIRE in the differentiation program of thymic epithelial cells in the medulla 胸腺髄質上皮細胞の分化におけるAIREの役割 科学評論社 Clinical immunology & allergology 臨床免疫・アレルギー科 1881-1930 56 1 90 96 20110700 mouri/misc/53033610 松本満 廣田史子 毛利安宏 松島明美 2章 免疫染色:酵素抗体法を用いた免疫組織染色 注目のバイオ実験シリーズ「改訂版・抗体実験マニュアル」(羊土社) 40 49 20080000 mouri/misc/53030271 毛利 安宏 松本 満 自己免疫疾患発病におけるAIREの役割 Annual Review 免疫 2007 204 211 20070000 mouri/misc/53033603 KINOSHITA Takatoshi 木下 隆利 MOURI Yasuhiro 毛利 安宏 The High Orientation of Polypeptide in the Monolayer and the Self-Oscillation ポリペプチド分子膜の高度配向化と自励振動 Amphiphilic polypeptides, poly (γ-methyl L-glutamate) containing β-cyclodextrin as active end group (PMG<SUB>n</SUB>-CyD ; n=19, 24, 34) were prepared. The spectra of circular dichroism spectroscopy showed a-helical conformation of the PMG moiety. At the n-hexane/water interface, molecules of PMGn-CyD formed a stable monolayer. Interfacial pressure-area (ϖ-A) isotherms suggested molecules of PMG<SUB>n</SUB>-CyD to be oriented almost normal to the n-hexane/water interface. When α-helical rods were oriented almost normal to the interface, 2-<I>P</I>-tolidilnyl-naphtalene-6-sulfonate (TNS) added as a guest molecule for CyD to the water phase under the monolayer caused fluctuation in interfacial pressure. Periodic movement of the PMG<SUB>n</SUB>-CyD monolayer due to the binding and release of guest molecules across the n-hexane/water interface was considered the reason for this. 疎水性ポリペプチドの分子鎖末端に分子認識能を有する親水性β-シクロデキストリンを配した両親媒性ポリペプチド (PMG<SUB>n</SUB>-CyD;重合度n=19, 24, 34) を調製し, 油/水界面における同単分子膜の構造及び機能を評価した．界面圧-面積 (ϖ一A) 測定の結果, PMG<SUB>n</SUB>-CyDはn-ヘキサン/水界面で安定な単分子膜を形成し, 界面圧を制御してPMG<SUB>n</SUB>-CyDを垂直方向に配向させることを可能にした．さらに, PMG<SUB>n</SUB>-CyD分子を界面に対して垂直方向に配向させた状態で, 水相にCyDのゲスト分子である2-P-トルイジニルナフタレン-6-スルホン酸カリウム塩 (TNS) を添加したところ, 界面圧の自発的な振動が誘起された．この振動現象に対し, PMG<SUB>n</SUB>-CyDとゲスト分子が結合・解離を繰り返すことにより, 膜ドメインがn-ヘキサン/水界面付近を周期的に移動するという機構を提案した． Japan Oil Chemists' Society 公益社団法人 日本油化学会 Oleoscience オレオサイエンス 2187-3461 1 9 943 948 20010000 10.5650/oleoscience.1.943 1390001204482952192 mouri/presentations/53625504 Natsumi Fujiwara Chen Siqi Yasuhiro Mouri Yuki Matsumura Ryo Kanamura Kumiko Kamada Yoshiko Yamamura YAGI Sayaka Naito Kurio Yoshiaki Kitamura Yasusei Kudo Diversity of Site-Specific Oral Microbiota in Oral Cancer. IADR/PER General Session, Barcelona, Spain 20250600 mouri/presentations/53625493 Siqi chen Natsumi Fujiwara Yasuhiro Mouri Yasusei Kudo Oral Cancer Microenvironment Influences Fusobacterium nucleatum Biofilm Formation. IADR/PER General Session & Exhibition, Barcelona, Spain 20250600 mouri/presentations/53625521 Yasuhiro Mouri Yasusei Kudo Inter-tumor heterogeneity based on EMT state in HNSCC. International Conference on Craniofacial Pathology & Biology, Tamil Nadu, India 20221000 mouri/presentations/53625575 Hitoshi Nishijima Yasuhiro Mouri Junko Morimoto Mitsuru Matsumoto Paradoxical development of polymyositis-like autoimmunity through augmented expression of human AIRE in mice. Controversies in Rheumatology and Autoimmunity 2017, Bologna, Italy 20170300 mouri/presentations/53625565 Hitoshi Nishijima Yasuhiro Mouri Junko Morimoto Mitsuru Matsumoto Paradoxical development of polymyositis-like autoimmunity through augmented expression of AIRE. 7th International Workshop of Kyoto T Cell Conference, Kyoto, Japan 20170300 mouri/presentations/53625582 Hiroshi Kawano Hitoshi Nishijima Junko Morimoto Yasuhiro Mouri Mitsuru Matsumoto Aire expression is inherent to all medullary thymic epithelial cells during their differentiation program. The 4th European Congress of Immunology, Vienna, Austria 20150900 mouri/presentations/53625618 Mitsuru Matsumoto Hiroshi Kawano Hitoshi Nishijima Junko Morimoto Yasuhiro Mouri Yasuhiko Nishioka Aire expression is inherent properties of all medullary thymic epithelial cells during their differentiation program. Venice Thymus Meeting 2015, Venice, Italy 20150400 mouri/presentations/53625628 Hitoshi Nishijima Junko Morimoto Hiroshi Kawano Yasuhiro Mouri Koichi Ikuta 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 20140400 mouri/presentations/53625632 Mitsuru Matsumoto Junko Morimoto Hiroshi Kawano Yasuhiro Mouri 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 20140300 mouri/presentations/53625642 Mitsuru Matsumoto Yumiko Nishikawa Yasuhiro Mouri Hitoshi Nishijima Temporal lineage tracing of Aire-expressing cells reveals a requirement of Aire for their maturation program. 15th ICI2013, Milan, Italy 20130800 mouri/presentations/53625652 Mitsuru Matsumoto Yumiko Nishikawa Hitoshi Nishijima Minoru Matsumoto Fumiko Hirota Satoru Takahashi Hervé Luche Hans Fehling Joerg 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 20130600 mouri/presentations/53625674 Mitsuru Matsumoto Yumiko Nishikawa Yasuhiro Mouri 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 20130500 mouri/presentations/53625688 Yumiko Nishikawa Yasuhiro Mouri Hitoshi Nishijima 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 20130400 mouri/presentations/53625705 Mitsuru Matsumoto Yumiko Nishikawa Yasuhiro Mouri 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 20130300 mouri/presentations/53625708 Mitsuru Matsumoto Yumiko Nishikawa Yasuhiro Mouri Fumiko Hirota Hitoshi Nishijima Temporal fate-mapping reveals essential roles of Aire in the maturation program of mTECs. ThymUS 2012, Florida, USA 20121100 mouri/presentations/53625714 Mitsuru Matsumoto Yumiko Nishikawa Yasuhiro Mouri Hitoshi Nishijima Functional analysis of Aire, a gene responsible for the hereditary type of autoimmune disease. Days of Molecular Medicine 2012, Wien, Austria 20121000 mouri/presentations/53625720 Mitsuru Matsumoto Yumiko Nishikawa Yasuhiro Mouri Hitoshi Nishijima Aire controls organization of thymic microenvironment for the establishment of self tolerance. European Congress of Immunology 2012, Glasgow, Scotland 20120900 mouri/presentations/53625727 Yasuhiro Mouri Yumiko Nishikawa Hitoshi Nishijima 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 20120300 mouri/presentations/53625741 Hitoshi Nishijima Yasuhiro Mouri Yumiko Nishikawa Mitsuru Matsumoto Cell-cycle dependent phosphorylation of AIRE protein exogenously expressed in HeLa cells. 4th International Conference on Drug Discovery & Therapy, Dubai, UAE 20120200 mouri/presentations/53625751 Mitsuru Matsumoto Yumiko Nishikawa Yasuhiro Mouri Hitoshi Nishijima Expression of Aire, a gene responsible for autoimmune disease, in ES cells. Cell Symposia: Stem Cell Programming & Re-programming, Lisbon, Portugal 20111200 mouri/presentations/53625756 Mitsuru Matsumoto Yasuhiro Mouri Yumiko Nishikawa Hitoshi Nishijima Aire-dependent organization of thymic microenvironment for the establishment of self tolerance. 5th Asian Congress on Autoimmunity, Suntec City, Singapore 20111100 mouri/presentations/53625762 Mitsuru Matsumoto Yasuhiro Mouri Yumiko Nishikawa 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 20110900 mouri/presentations/53625772 Yasuhiro Mouri Masashi Yano Miho Shinzawa Yusuke Shimo Yumiko Nishikawa Koji Tamada Lieping Chen Josef M. Penninger Jun-ichiro Inoue Taishin Akiyama Mitsuru Matsumoto Lymphotoxin signal promotes thymic organogenesis by eliciting RANK expression in the embryonic thymic stroma. 13th International TNF Conference, TNF 2011, Hyogo, Japan 20110500 mouri/presentations/53625765 Mitsuru Matsumoto Yumiko Nishikawa Yasuhiro Mouri Hitoshi Nishijima Aire-dependent organization of thymic microenvironment for the establishment of self tolerance. EUThyme-Rolduc Meeting, Leeuwenhorst, The Netherlands 20110500 mouri/presentations/53625782 Yumiko Nishikawa Yasuhiro Mouri Hitoshi Nishijima Mitsuru Matsumoto Aire-dependent organization of thymic microenvironment for the establishment of self-tolerance. Cutting Edge Immunology and its Clinical Application, Hulshort, The Netherlands 20110300 mouri/presentations/53625780 Mitsuru Matsumoto Yumiko Nishikawa Hitoshi Nishijima Yasuhiro Mouri Role of Aire in the organization of thymic microenvironment. Controversies in Rheumatology and Autoimmunity (CORA 2011), Florence, Italy 20110300 mouri/presentations/53625794 Yumiko Nishikawa Yasuhiro Mouri 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, Hyogo, Japan 20100800 mouri/presentations/53625792 Yasuhiro Mouri Yumiko Nishikawa Mitsuru Matsumoto Aire in thymic epithelial cells in the medulla controls developmental process of thymocytes. 14th International Congress of Immunology, Hyogo, Japan 20100800 mouri/presentations/53625800 Yasuhiro Mouri Mitsuru Matsumoto Aire in thymic epithelial cells in the medulla controls developmental process of thymocytes. 7th International Congress on Autoimmunity, Ljubljana, Slovenia 20100500 mouri/presentations/53625807 Mitsuru Matsumoto Yumiko Nishikawa Fumiko Hirota Yasuhiro Mouri AIRE and autoimmune disease. The 19th International Rheumatology Symposium, Hyogo, Japan 20100400 mouri/presentations/53625852 Yasuhiro Mouri Masashi Yano Mitsuru Matsumoto Roles of NIK in thymic epithelial cells for the establishment of central tolerance. 12th International TNF Conference, Madrid, Spain 20090400 mouri/presentations/53625820 Mitsuru Matsumoto Yumiko Nishikawa Masashi Yano Fumiko Hirota Yasuhiro Mouri Aire-dependent organization of thymic microenvironment. International KTCC 2009, Kyoto, Japan 20090100 mouri/presentations/53625883 Yasuhiro Mouri Mitsuru Matsumoto Aire in thymic stroma controls early thymopoiesis. Rolduc Workshop on T cell Biology, Kerkrade, The Netherlands 20070500