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Hui Shao, Yan Ke, Guomin Jiang, Henry J. Kaplan, Deming Sun; IL-22 Has A Suppressive Effect In Experimental Autoimmune Uveitis (EAU). Invest. Ophthalmol. Vis. Sci. 2011;52(14):2952.
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Previous studies have shown that while IL-17+ IRBP-specific T cells have a strong pathogenic effect in EAU, the major cytokine produced by these cells-IL-17 does not always have proinflammatory effects. IL-22, one of the cytokines chiefly produced by IL-17+ CD4 cells, has also been reported to have paradoxical effects during tissue inflammation. We wanted to determine the role of IL-22 in the pathogenesis of EAU.
Uveitis was induced in B10RIII mice by immunization with the 161-180 peptide of interphotoreceptor retinoid-binding protein (IRBP). Then the mice received two i.p. injections of recombinant IL-22 on days 4 and 8 after immunization. Ocular inflammation was examined by funduscopy and histology. Proliferation, cytokine production and disease inducing ability of responder T cells from IL-22 treated or non-treated mice were determined and compared. Expression of IL-22 receptor (IL-22R) on immune cell subsets was examined by RT-qPCR. Effects of IL-22 on APC both in vivo and in vitro were examined by their production of cytokines, expression of costimulatory molecules and interaction with IRBP-T cells.
Administration of IL-22 significantly inhibited the development of EAU. Mice treated with IL-22 generated decreased numbers of IFN-γ autoreactive T cells but increased numbers of Foxp3+ regulatory T cells, which was due to regulatory APCs induced by IL-22. These APCs expressed high levels of PD-L1 and produced increased amounts of IL-10 and TGF-β. Moreover, IRBP specific T cells in the presence IL-22 treated APCs lost their uveitogenic intensity, but acquired immunosuppressive activity. These T cells suppressed EAU induced by pathogenic IRBP effector T cells.
Treatment of animals undergoing induction of EAU with IL-22 inhibits the development of EAU-i.e. it is anti-inflammatory. This effect is mediated by regulatory APCs that bestow effector T cells with regulatory activities.
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