| Budget Amount *help |
¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
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| Outline of Final Research Achievements |
We discovered bi-allelic RORC loss-of-function mutations in seven individuals from three kindreds of different ethnic origins with both candidiasis and mycobacteriosis. The lack of functional RORγT resulted in the absence of IL-17A/F-producing T cells in these individuals, probably accounting for their chronic candidiasis. Unexpectedly, leukocytes from RORγT-deficient individuals also displayed an impaired IFN-γ response to Mycobacterium. This principally reflected profoundly defective IFN-γ production by circulating γδ T cells and CD4+CCR6+ CXCR3+ αβT cells. We thus discovered that both mucocutaneous immunity to Candida and systemic immunity to Mycobacterium require RORγT in human （Okada S, et al. Science 349: 606-13, 2015).
We performed functional assay based on systematic alanine-scanning mutagenesis of human STAT1, which can be used to estimate the gain-of-function or loss-of-function status of nonsynonymous mutations (manuscript in preparation).
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