2019 Fiscal Year Final Research Report
Molecular Mechanism of Autoimmune Germinal Center Reaction and a New Therapeutic Strategy for Autoimmunity
| Project/Area Number |
18K19648
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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 57:Oral science and related fields
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| Research Institution | The University of Tokushima |
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Principal Investigator |
ISHIMARU Naozumi 徳島大学, 大学院医歯薬学研究部(歯学域), 教授 (60314879)
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| Co-Investigator(Kenkyū-buntansha) |
新垣 理恵子 徳島大学, 大学院医歯薬学研究部(歯学域), 准教授 (00193061)
工藤 保誠 徳島大学, 大学院医歯薬学研究部(歯学域), 准教授 (50314753)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Keywords | 自己免疫疾患 / 自己抗体 / Tfh細胞 / GC反応 / シェーグレン症候群 |
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| Outline of Final Research Achievements |
Follicular helper T (Tfh) cells are known to contribute to various immune responses as well as to the pathogenesis of several immune diseases. However, the precise mechanism underlying the onset or development of autoimmunity via Tfh cells remains unclear. Here, the detailed relationship between autoimmune disease and Tfh cells was analyzed using a murine model for Sjögren’s syndrome (SS) wherein the mice underwent neonatal thymectomy (Tx). The severity of the autoimmune lesions was correlated with the number of Tfh cells detected in the spleen of the SS model mice. Comprehensive gene analysis revealed that several genes associated with Tfh cell differentiation, including achaete-scute homologue 2 (Ascl2), were upregulated in peripheral CD25－ CD4+ T cells in SS model mice compared to those in control mice. In conclusion, our results indicate that abnormal Tfh cell differentiation via Ascl2 regulation might contribute to the pathogenesis of autoimmunity.
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| Free Research Field |
病理学
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| Academic Significance and Societal Importance of the Research Achievements |
自己免疫疾患は自身の臓器や細胞が免疫反応の標的となる疾患であり、自己と非自己を厳密に区別するはずの免疫システムの適切な機能から明らかに逸脱している。全身どの臓器も標的となり、単一の原因ではなく多因子による発症機序が存在しているため、病態メカニズムは複雑で、自己免疫疾患の診断は困難な場合があり、病因論に基づいた根本的な治療法の開発には至っていないのが現状である。本研究では、自己免疫性胚中心反応という新たな概念を提唱するとともに、その詳細な機構を明らかにし、病態と自己抗体の新たな関係を解明した点で、重要な内容を含む研究であり、今後、臨床応用への可能性が十分示された。
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