| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Research Abstract |
Th17 cells play a pathogenic role in autoimmune diseases. It has been shown that IL-6- and/or IL-21-mediated activation of Stat3 is essential for the expression of RORgammat, which is a lineage-specifying transcription factor of Th17 cells. In this study, we find that Sox5 and c-Maf are induced in Th17 cells in a Stat3-dependent manner. Sox5 together with c-Maf induce Th17 cell differentiation as downstream effectors of Stat3 and as upstream inducers of RORgammat. In addition, we find that T cell-specific Sox5-deficient mice exhibit impaired Th17 cell differentiation and are resistant to experimental autoimmune encephalomyelitis and delayed-type hypersensitivity. Taken together, these results suggest that Sox5 and c-Maf cooperatively induce Th17 cell differentiation via the induction of RORgammat as downstream targets of Stat3.
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