2015 Fiscal Year Final Research Report
Regulation of autoantibody production by regulatory T cells expressing anergy-associated genes
| Project/Area Number |
25461493
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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 |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 制御性T細胞 / 自己抗体 / 全身性エリテマトーデス / LAG3 / Egr2 / TGF-β |
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| Outline of Final Research Achievements |
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and associated with a wide range of clinical manifestations. Early growth response gene-2 (EGR2), a zinc-finger transcription factor, is known to affect susceptibility to SLE in human. We previously reported CD4+CD25-Foxp3-LAG3+ regulatory T cells (LAG3 Tregs) that characteristically express Egr2. In this study, we revealed that LAG3 Tregs, but not CD4+CD25+ Tregs, produce enormous amounts of TGF-β3 in an Egr2-dependent manner. TGF-β3 effectively suppressed autoantibody production from B cells through suppression of Syk, STAT6, and NF-κB pathways. Intriguingly, Egr3 was able to compensate the function of Egr2. These findings elucidated the mechanisms of T cell anergy-associated gene Egr2-mediated regulation of humoral immunity.
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| Free Research Field |
医歯薬学
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