Differential roles for IFN-γ and IL-17 in experimental autoimmune uveoretinitis

IL-17-producing CD4+ T cells, so called Th17 cells, constitute a newly identified inflammatogenic cell population, which is critically involved in some inflammatory diseases. To explore the role of Th17 cells in murine experimental autoimmune uveoretinitis (EAU), a model of human autoimmune uveitis where Th1 responses predominantly participate in the pathogenesis, IL-17−/− mice were immunized with interphotoreceptor retinoid-binding protein peptide 1–20 for disease induction. Funduscopic examination revealed that EAU was induced in IL-17−/− mice just like in wild-type (WT) mice at early phases of the disease. However, at later/maintenance phases, the severity was significantly reduced in IL-17−/− mice. Expression of IFN-γ and MCP-1 was comparable between WT and IL-17−/− mice during the time course. In vivo blockade of IFN-γ and IL-4 resulted in exacerbation of EAU at later phases with augmented IL-17 production. Taken together, our data demonstrated that IL-17/Th17 participates in the late phases of EAU and also that Th1 and Th17 responses are differentially required for EAU.