| Project/Area Number |
26461462
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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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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Shoda Hirofumi 東京大学, 医学部附属病院, 助教 (20529036)
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| Research Collaborator |
NAGAFUCHI Yasumo 東京大学, 医学部附属病院, 助教
SAKURAI Keiichi 東京大学, 医学部附属病院, 非常勤医員
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 関節リウマチ / T細胞 / BiP / T細胞受容体 / 自己抗原 / 抗酸菌 / 制御性T細胞 |
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| Outline of Final Research Achievements |
HLA-DRB1 is the most potent genetic risk locus in rheumatoid arthritis (RA). Autoantigens are presented on HLA-DRB1 and activate CD4+ T cells, which contribute to RA pathogenesis. Here, we analyzed T cell receptor (TCR) repertoire by next generaton sequencing (NGS), and demonstrated that a significant correlation between HLA-DRB1 and TCR repertoires.
We identified HLA-DRB1*0405 epitopes derived from autoantigen, BiP. In RA patients, BiP-specific effector T cells were proliferated and BiP-specific regulatory T cells controled thier proliferations. Tolerance to BiP peptides ameliorated mouse model of arthritis. Furthermore, Mycobacterium HSP70-specific T cell responses were increased in RA, and molecular mimicry is speculated on the basis of autoimmunity to BiP. Taken together, we proposed the new therapeutic approach for RA by autoantigen-specific T cell regulation.
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