Involvement of the Wnt5a-Ror2 signaling in colitis

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590378
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Osaka University
• Principal Investigator: SATO AKIRA 大阪大学, 医学(系)研究科(研究院), 助教 (70464302)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: Wnt5a-Ror2シグナル / 腸管炎症 / 樹状細胞 / Th1細胞 / IFN-γ-STAT1シグナル / β-カテニン非依存性経路 / IL-12

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.

Free Research Field

分子生物学