Studies on the mechanisms underlying autoimmune ambivalence
| Project/Area Number |
18K19564
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
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| Research Institution | The University of Tokushima |
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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)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | 自己免疫疾患 / Aire / 多発性筋炎 / I型糖尿病 / 抗原提示細胞 / 樹状細胞 / 骨髄移植 |
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| Outline of Final Research Achievements |
Roles of Aire in the pathogenesis of tissue-specific autoimmune diseases remain elusive. In order to elucidate the function of Aire, we have established transgenic mice expressing Aire. Aire-Tg which express Aire under the control of MHC-II promoter showed an ambivalent phenotype with polymyositis-like autoimmunity and resistance to type I diabetes (T1D). We have revealed that polymyositis-like autoimmunity was caused by the combination of mTECs and BM-APCs with the use of BM transfer. In contrast, T1D resistance was mediated by BM-APCs. Finally, we have discovered that over-expression of Aire in DCs resulted in the reduced numbers of Xcr1-positive DCs, that play a critical role in the development of T1D. Thus, our studies for the first time uncovered a dual role of Aire in the induction (polymyositis-like autoimmunity) and suppression of autoimmunity (development of T1D).
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| Academic Significance and Societal Importance of the Research Achievements |
多発性内分泌疾患I型（APSI）の原因遺伝子Aireは自己寛容の成立機構に必須の役割を担う。本研究ではmTECやBM-APCなどの抗原提示細胞におけるAireの過剰発現が、どのようなメカニズムによって自己免疫病態の発生と修復（両価性）をもたらすかを明らかにし、それによってAireの本質的な機能解明を図った。Aireの過剰発現によるI型糖尿病抵抗性の獲得機構のメカニズムについてはXcr1陽性DCの減少がその原因であることを突き止めた。さらに、Aireの過剰発現によって多発性筋炎様病態が観察された事実から、ヒトの多発性筋炎においてもAireの過剰発現が病気の原因であるという大胆な仮説を検証した。
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Report
(3 results)
Research Products
(22 results)
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[Book] Thymus Transcriptome and Cell Biology2019
Author(s)
Minoru Matsumoto, Pedro M. Rodrigues, Laura Sousa, Koichi Tsuneyama, Mitsuru Matsumoto, Nuno L. Alves
Total Pages
31
Publisher
Springer International Publishing
ISBN
9783030120399
Related Report
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