title: IL-33 attenuates EAE by suppressing IL-17 and IFN-γ production and inducing alternatively activated macrophages.
abstract: Interleukin (IL)-33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated disorders. High levels of IL-33 are expressed by the central nervous system (CNS) suggesting a potential role of IL-33 in autoimmune CNS diseases. We have investigated the expression and function of IL-33 in the development of experimental autoimmune encephalomyelitis (EAE) in mice. We report here that IL-33 and its receptor ST2 (IL-33Rα) are highly expressed in spinal cord tissue, and ST2 expression is markedly increased in the spinal cords of mice with EAE. Furthermore, ST2-deficient (ST2(-/-) ) mice developed exacerbated EAE compared with wild-type (WT) mice while WT, but not ST2(-/-)  EAE mice treated with IL-33 developed significantly attenuated disease. IL-33-treated mice had reduced levels of IL-17 and IFN-γ but produced increased amounts of IL-5 and IL-13. Lymph node and splenic macrophages of IL-33-treated mice showed polarization toward an alternatively activated macrophage (M2) phenotype with significantly increased frequency of MR(+) PD-L2(+)  cells. Importantly, adoptive transfer of these IL-33-treated macrophages attenuated EAE development. Our data therefore demonstrate that IL-33 plays a therapeutic role in autoimmune CNS disease by switching a predominantly pathogenic Th17/Th1 response to Th2 activity, and by polarization of anti-inflammatory M2 macrophages.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK. huirong.jiang@strath.ac.uk
authors.forename: Hui-Rong
authors.initials: HR
authors.lastname: Jiang
authors.forename: Marija
authors.initials: M
authors.lastname: Milovanović
authors.forename: Debbie
authors.initials: D
authors.lastname: Allan
authors.forename: Wanda
authors.initials: W
authors.lastname: Niedbala
authors.forename: Anne-Galle
authors.initials: AG
authors.lastname: Besnard
authors.forename: Sandra Y
authors.initials: SY
authors.lastname: Fukada
authors.forename: Jose C
authors.initials: JC
authors.lastname: Alves-Filho
authors.forename: Dieudonnée
authors.initials: D
authors.lastname: Togbe
authors.forename: Carl S
authors.initials: CS
authors.lastname: Goodyear
authors.forename: Christopher
authors.initials: C
authors.lastname: Linington
authors.forename: Damo
authors.initials: D
authors.lastname: Xu
authors.forename: Miodrag L
authors.initials: ML
authors.lastname: Lukic
authors.forename: Foo Y
authors.initials: FY
authors.lastname: Liew
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology; D000067596:Interleukin-33; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology
chemical_list: C506535:Il33 protein, mouse; D020381:Interleukin-17; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin; D007371:Interferon-gamma