Inhibitory cytokine-producing Treg-mediated control of autoimmunity
| Project/Area Number |
16K15510
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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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 |
Fujio Keishi 東京大学, 医学部附属病院, 教授 (70401114)
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| Research Collaborator |
KOMAI TOSHIHIKO 東京大学, 医学部附属病院, 特任臨床医 (50803938)
INOUE MARIKO 東京大学, 医学部附属病院, 特任臨床医 (60816601)
MORITA KAORU 東京大学, 医学部附属病院, 特任臨床医
TERUYA SHUZO 東京大学, 医学部附属病院, 特任臨床医
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 制御性T細胞 / TGF-β / LAG3 / TGF-β3 / IL-10 / TGF-beta3 / Egr2 / サイトカイン / TGF-beta / ノックアウトマウス |
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| Outline of Final Research Achievements |
The aim of this project was to elucidate the role of inhibitory cytokine in regulatory T cell (Treg)-mediated control of autoimmunity. Although inhibitory cytokines, such as transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) play major roles in maintaining immune homeostasis, therapeutic application of inhibitory cytokines remains limited due to their pleiotropic and context-dependent effects. In this study, we reveled that a combination of TGF-β and IL-10, but not single cytokine, is required to suppress B cell activation induced by toll-like receptor (TLR) stimulation both in vitro and in vivo. The combination of these two inhibitory cytokines synergistically suppressed cellular energetics of both glycolysis and oxidative phosphorylation in B cells. By exploiting the cytokine synergy-mediated immune suppression, they may provide a new therapeutic method in autoantibody-mediated autoimmune diseases.
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Report
(3 results)
Research Products
(15 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
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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