2014 Fiscal Year Final Research Report
Analysis of Egr2-expressing regulatory T cells in mice and human
| Project/Area Number |
24390252
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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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, 講師 (70401114)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 自己免疫疾患 / 制御性T細胞 / TGF-beta |
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| Outline of Final Research Achievements |
We previously described that CD4+CD25-LAG3+regulatory T cells(LAG3+ Treg) are regulated by Egr2, a zinc-finger transcription factor required for the
induction of T-cell anergy.We herein demonstrate that LAG3+Treg produce high amounts ofTGF-beta3 in an Egr2- and Fas-dependent manner. LAG3+Treg require TGF-beta3 to suppress B-cell responses in a murine model of lupus. Moreover, TGF-beta3- and LAG3+Treg-mediated suppression requires PD-1 expression on B cells. We also show that TGF-beta3-expressing human LAG3+Treg suppress antibody production and that SLE patients exhibit decreased frequencies of LAG3+Treg. These results clarify the mechanism of B-cell regulation and suggest therapeutic strategies.
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| Free Research Field |
アレルギー・リウマチ学
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