Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2012: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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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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