| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
IL-17-producing Th17 cells comprise heterogeneous subsets exhibiting distinct pathogenicity. Although pathogenic and non-pathogenic Th17 subsets share a common Th17 transcriptional program composed of BATF, IRF4, STAT3, and RORgt, transcriptional regulatory mechanisms specific to each of these distinct Th17 subsets remain largely unknown. Here we show that an AP-1 transcription factor, JunB, is essential for induction of RORgt by facilitating DNA-binding of BATF, IRF4 and STAT3 at the Rorc locus in IL-23-dependent pathogenic Th17 cells, but not in TGF-b1-dependent non-pathogenic Th17 cells. Indeed, JUNB deficient T cells lose their ability to induce Th17-mediated experimental autoimmune encephalomyelitis (EAE) and colitis, but gut-resident Th17 cells are probably generated in a JUNB-independent manner. The selective requirement of JUNB for pathogenic Th17 differentiation suggests that the JUNB-dependent pathway may be a specific therapeutic target for autoimmune diseases.
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