Differential roles for IFN-gamma and IL-17 in experimental autoimmune uveoretinitis.
IL-17-producing CD4(+) T cells, so called T(h)17 cells, constitute a newly identified inflammatogenic cell population, which is critically involved in some inflammatory diseases. To explore the role of T(h)17 cells in murine experimental autoimmune uveoretinitis (EAU), a model of human autoimmune uveitis where T(h)1 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-gamma and MCP-1 was comparable between WT and IL-17(-/-) mice during the time course. In vivo blockade of IFN-gamma and IL-4 resulted in exacerbation of EAU at later phases with augmented IL-17 production. Taken together, our data demonstrated that IL-17/T(h)17 participates in the late phases of EAU and also that T(h)1 and T(h)17 responses are differentially required for EAU.
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005136:Eye Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D012173:Retinitis / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology; D012177:Retinol-Binding Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D018417:Th1 Cells; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology; D000099214:Retinol-Binding Proteins, Interstitial
D016207:Cytokines; D005136:Eye Proteins; D007371:Interferon-gamma; D020381:Interleukin-17; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial