| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Outline of Final Research Achievements |
It has been suggested that post-natal abnormalities in Wnt5a signaling are involved in inflammatory diseases, however the mechanism is not well understood. I examined the role of Wnt5a signaling in intestinal immunity using conditional knockout mice for Wnt5a and its receptor Ror2. Removing Wnt5a or Ror2 suppressed dextran sodium sulfate (DSS)-induced colitis. It also attenuated the DSS-dependent increase in inflammatory cytokine expression and suppressed IFN-γ-producing CD4+ Th1 cells in the colon. Wnt5a was expressed by stromal fibroblasts in ulcerative lesions in DSS-treated mice and inflammatory bowel disease patients. In vitro experiments demonstrated that the Wnt5a-Ror2 signaling axis augmented the dendritic cell (DC) priming effect of IFN-γ, leading to enhanced IL-12 expression. Taken together, these results suggest that the Wnt5a produced by stromal fibroblasts promotes IFN-γ signaling, leading to IL-12 expression in DCs, and thereby inducing Th1 polarization in colitis.
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