Antigen specific therapy for rheumatoid arthritis
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 |
Section | 一般 |
Research Field |
Collagenous pathology/Allergology
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Research Institution | The University of Tokyo |
Principal Investigator |
Shoda Hirofumi 東京大学, 医学部附属病院, 助教 (20529036)
|
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
|
Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
|
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)
|
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 |
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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Report
(4 results)
Research Products
(8 results)
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[Journal Article] Identification of tonsillar CD4+CD25-LAG3+ T cells as naturally occurring IL-10-producing regulatory T cells in human lymphoid tissue.2017
Author(s)
Sumitomo S, Nakachi S, Okamura T, Tsuchida Y, Kato R, Shoda H, Furukawa A, Kitahara N, Kondo K, Yamasoba T, Yamamoto K, Fujio K.
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Journal Title
Journal of Autoimmunity
Volume: 76
Pages: 75-84
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Enhanced gut homing receptor expression of unswitched memory B cells in rheumatoid arthritis.2017
Author(s)
agafuchi Y, Shoda H, Sumitomo S, Nakachi S, Kato R, Tsuchida Y, Tsuchiya H, Sakurai K, Hanata N, Tateishi S, Kanda H, Fujio K, Yamamoto K.
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Journal Title
Clin Exp Rheumatol
Volume: 35
Pages: 354-355
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Immunophenotyping of rheumatoid arthritis reveals a linkage between HLA-DRB1 genotype, CXCR4 expression on memory CD4(+) T cells, and disease activity.2016
Author(s)
Nagafuchi Y, Shoda H, Sumitomo S, Nakachi S, Kato R, Tsuchida Y, Tsuchiya H, Sakurai K, Hanata N, Tateishi S, Kanda H, Ishigaki K, Okada Y, Suzuki A, Kochi Y, Fujio K, Yamamoto K
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Journal Title
Scientific reports
Volume: 6
Issue: 1
Pages: 29338-29338
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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