IL-33 attenuates the development of experimental autoimmune uveitis

Barbour, Mark and Allan, Debbie and Xu, Heping and Pei, Cheng and Chen, Mei and Niedbala, Wanda and Fukada, Sandra Y and Besnard, Anne-Galle and Alves-Filho, Jose C and Tong, Xiaoguang and Forrester, John V and Liew, Foo Yew and Jiang, Hui-Rong (2014) IL-33 attenuates the development of experimental autoimmune uveitis. European Journal of Immunology, 44 (11). pp. 3320-3329. ISSN 0014-2980

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    Abstract

    Interleukin-33 (IL-33) is associated with several important immune-mediated disorders. However, its role in uveitis, an important eye inflammatory disease, is unknown. Here, we investigated the function of IL-33 in the development of experimental autoimmune uveitis (EAU). IL-33 and IL-33 receptor (ST2) were expressed in murine retinal pigment epithelial (RPE) cells in culture, and IL-33 increased the expression of Il33 and Mcp1 mRNA in RPE cells. In situ, IL-33 was highly expressed in the inner nuclear cells of the retina of naïve mice, and its expression was elevated in EAU mice. ST2-deficient mice developed exacerbated EAU compared with WT mice, and administration of IL-33 to WT mice significantly reduced EAU severity. The attenuated EAU in IL-33-treated mice was accompanied by decreased frequency of IFN-γ+ and IL-17(+) CD4+ T cells and reduced IFN-γ and IL-17 production but with increased frequency of IL-5(+) and IL-4(+) CD4 T cells and IL-5 production in the draining lymph node and spleen. Macrophages from the IL-33-treated mice show a significantly higher polarization toward an alternatively activated macrophage phenotype. Our results therefore demonstrate that the endogenous IL-33/ST2 pathway plays an important role in EAU, and suggest that IL-33 represents a potential option for treatment of uveitis.