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We have previously reported that IL-17+ interphotoreceptor retinoid-binding protein (IRBP) 161–180-specific T cells have a strong pathogenic effect in experimental autoimmune uveitis (EAU) induced in B10RIII mice; however, this pathogenic activity is not solely attributable to the major cytokine, IL-17, produced by these cells. To determine whether other cytokines produced by Th17 cells show a stronger association with their pathogenic activity, we studied the role of IL-22 in EAU. IL-22 is one of the major cytokines produced by these cells. Our results showed that administration of small doses of IL-22 to EAU-susceptible mice significantly reduced the severity of EAU. In addition, mice treated with IL-22 generated decreased numbers of IFN-γ+ and IL-17+ uveitogenic T cells, but increased numbers of Foxp3+ regulatory T cells. Mechanistic studies showed that the effect of the injected IL-22 was on CD11b+ APCs …