IL-33 attenuates the development of experimental autoimmune uveitis

Mark Barbour, Debbie Allan, Heping Xu, Cheng Pei, Mei Chen, Wanda Niedbala, Sandra Y Fukada, Anne-Galle Besnard, Jose C Alves-Filho, Xiaoguang Tong, John V Forrester, Foo Yew Liew, Hui-Rong Jiang

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

Abstract

Interleukin (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 towards an alternatively-activated macrophage (M2) 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.
Original languageEnglish
Pages (from-to)3320-3329
Number of pages10
JournalEuropean Journal of Immunology
Volume44
Issue number11
Early online date18 Oct 2014
DOIs
Publication statusPublished - Nov 2014

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