title: IL-33 attenuates the development of experimental autoimmune uveitis.
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.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Barbour
authors.forename: Debbie
authors.initials: D
authors.lastname: Allan
authors.forename: Heping
authors.initials: H
authors.lastname: Xu
authors.forename: Cheng
authors.initials: C
authors.lastname: Pei
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
authors.forename: Wanda
authors.initials: W
authors.lastname: Niedbala
authors.forename: Sandra Y
authors.initials: SY
authors.lastname: Fukada
authors.forename: Anne-Galle
authors.initials: AG
authors.lastname: Besnard
authors.forename: Jose C
authors.initials: JC
authors.lastname: Alves-Filho
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Tong
authors.forename: John V
authors.initials: JV
authors.lastname: Forrester
authors.forename: Foo Yew
authors.initials: FY
authors.lastname: Liew
authors.forename: Hui-Rong
authors.initials: HR
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005123:Eye / Q000276:immunology / Q000473:pathology; D005136:Eye Proteins / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D000072179:Interleukin-1 Receptor-Like 1 Protein; D020381:Interleukin-17 / Q000096:biosynthesis; D000067596:Interleukin-33; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology
chemical_list: D005136:Eye Proteins; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D020381:Interleukin-17; D000067596:Interleukin-33; D015848:Interleukin-5; D007378:Interleukins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: Experimental autoimmune uveitis; Inflammation; Interleukin-33; Macrophages; T cells