Elucidation of the pathogenesis of autoimmune disease through the functional study of AIRE
Project/Area Number |
16H05342
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Collagenous pathology/Allergology
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Research Institution | The University of Tokushima |
Principal Investigator |
MATSUMOTO Mitsuru 徳島大学, 先端酵素学研究所(次世代), 教授 (60221595)
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Co-Investigator(Kenkyū-buntansha) |
森本 純子 徳島大学, 先端酵素学研究所(次世代), 助教 (20451396)
西嶋 仁 徳島大学, 先端酵素学研究所(次世代), 助教 (60425410)
毛利 安宏 徳島大学, 大学院医歯薬学研究部(医学系), 助教 (80464353)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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Keywords | 自己免疫疾患 / Aire / 遺伝子改変マウス / I型糖尿病 / 胸腺 / 樹状細胞 / 自己免疫 / AIRE |
Outline of Final Research Achievements |
Although AIRE deficiency is a rather rare autoimmune disease, it has an advantage where we can study the pathogenesis through creating the Aire-deficient mice. In order to reveal the bona fide pathogenesis of AIRE-dependent autoimmunity, elucidation of the target genes controlled by AIRE is essential. For this, we have established novel Aire-modified strains of mice. With the use of state-of-the-art technologies, we have studied the immunological function of AIRE. During this study, we unexpectedly found that over-expression of AIRE in antigen-presenting cells with the use of MHC-II promoter paradoxically induced the muscle-specific autoimmunity.
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Academic Significance and Societal Importance of the Research Achievements |
自己免疫疾患の原因は未だに不明だが、免疫システムが自分自身の身体を攻撃することによって惹起される難病である。自己免疫疾患には様々なタイプが存在するが、AIRE欠損症はAIREという単一遺伝子の機能異常によって引き起こされるため、他の自己免疫疾患に比べ、遺伝子改変マウスを用いて病態や新規治療法の開発などの研究に取り組むことが可能である。本研究では様々なタイプのAire遺伝子改変マウスを樹立し、AIRE遺伝子の機能障害によって、どのようなメカニズムによって自己免疫病態が発症するのかについて解析を試みた。また、AIRE遺伝子の働きを利用して、自己免疫病態を是正することも試みた。
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] Paradoxical development of polymyositis-like autoimmunity through augmented expression of autoimmune regulator (AIRE)2018
Author(s)
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
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Journal Title
J. Autoimmunity
Volume: 86
Pages: 75-92
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Aire Controls in Trans the Production of Medullary Thymic Epithelial Cells Expressing Ly-6C/Ly-6G2018
Author(s)
Junko Morimoto, Yumiko Nishikawa, Takumi Kakimoto, Kohei Furutani, Naoki Kihara, Minoru Matsumoto, Koichi Tsuneyama, Yuko Kozono, Haruo Kozono, Katsuto Hozumi, Kazuyoshi Hosomichi, Hitoshi Nishijima and Mitsuru Matsumoto
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Journal Title
J. Immunol
Volume: 201
Pages: 3244-3257
DOI
Related Report
Peer Reviewed
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[Journal Article] Identification of embryonic precursor cells that differentiate into thymic epithelial cells expressing autoimmune regulator2016
Author(s)
Akiyama N, Takizawa N, Miyauchi M, Yanai H, Tateishi R, Shinzawa M, Yoshinaga R, Kurihara M, Demizu Y, Yasuda H, Yagi S, Wu G, Matsumoto M, Sakamoto R, Yoshida N, Penninger JM, Kobayashi Y, Inoue J, Akiyama T.
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Journal Title
J. Exp. Med.
Volume: 213
Pages: 1441-1458
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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