| Project/Area Number |
26860745
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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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 |
Akahira Lisa 東京大学, 医学部附属病院, 助教 (70725192)
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | 自己反応性T細胞 / 免疫学的寛容 / 胸腺 / 自己免疫 / 膠原病 |
|---|
| Outline of Final Research Achievements |
Clonal deletion and Foxp3+ regulatory T cell lineage commitment are well-known as the fate of autoreactive thymocytes. However, other pathways have not been fully clarified yet. On the other hand, the mechanism of autoantibody production in human disease remains incompletely understood. Here, we show that autoreactive CD4+ T cells can differentiate into naturally occurring autoreactive B cell-helper T (natural TAH) cells, which are rendered anergic in vivo, in the thymus of gene-manipulated and wild-type mice. Natural TAH cells are defined as IL-21-producing Bcl-6+Helios+ Foxp3-PD-1+CD200+CXCR5-CD4+ T cells, and promote B cells to produce immunoglobulin. Although Bcl-6 is required for generation of natural TAH cells, they can be distinguished from traditional follicular helper T cells in self-reactivity, CXCR5 expression, and ontogeny. This new differential pathway into natural TAH cells might be a key regulator of autoimmune disease with autoantibodies.
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