2022 Fiscal Year Final Research Report
Development of a new treatment strategy for SLE by artificially restoring epigenomic memory in helper T cells
| Project/Area Number |
20K08815
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 全身性エリテマトーデス / 濾胞性ヘルパーT細胞 / 濾胞制御性ヘルパーT細胞 / 末梢性ヘルパーT細胞 / エピジェネティクス / サイトカイン |
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| Outline of Final Research Achievements |
In SLE patients, decreased IL-2 resulted in increased Tfh cells and decreased Tfr cells. IL-2 reduction in SLE patients was associated with genetic regulation of IL-2 by the disease susceptibility gene IL21-AS1. IL-2 induced the conversion of memory Tfh cells to functional Tfr cells by epigenetic regulation via activation of STAT3/STAT5. On the other hand, Tph cells increased in SLE, and their differentiation was induced by TGF-β3 produced from tissue macrophages, unlike Tfh cells, and promoted B cell differentiation and antibody production. These results suggest that IL-2 and TGF-β3, which are involved in the differentiation of pathological T cells in SLE, are novel therapeutic targets mediated by epigenome repair.
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| Free Research Field |
膠原病・リウマチ学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の結果は、SLEの病態においてT細胞の分化や機能の異常がゲノム異常により規定されるSLE特異的なエピゲノム記憶に基づく可能性を示唆する。これらを標的とした創薬はSLEの治療抵抗性難治性病態への新たな治療戦略に有望である。本研究は、免疫難病であるSLEへの疾患特異的治療の開発に重要な示唆を与え、医療および社会の発展に資するものである。
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