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- Title
IL-33 attenuates EAE by suppressing IL-17 and IFN-γ production and inducing alternatively activated macrophages.
- Authors
Jiang, Hui-Rong; Milovanović, Marija; Allan, Debbie; Niedbala, Wanda; Besnard, Anne-Galle; Fukada, Sandra Y.; Alves-Filho, Jose C.; Togbe, Dieudonnée; Goodyear, Carl S.; Linington, Christopher; Xu, Damo; Lukic, Miodrag L.; Liew, Foo Y.
- 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-33 Rα) 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.
- Publication
European Journal of Immunology, 2012, Vol 42, Issue 7, p1804
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201141947