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IL ‐33 attenuates EAE by suppressing IL ‐17 and IFN ‐γ production and inducing alternatively activated macrophages

2012; Wiley; Volume: 42; Issue: 7 Linguagem: Inglês

10.1002/eji.201141947

1521-4141

Hui‐Rong Jiang, Marija Milovanović, Debbie Allan, Wanda Niedbała, Anne‐Galle Besnard, Sandra Yasuyo Fukada, José C. Alves‐Filho, Dieudonnée Togbe, Carl S. Goodyear, Christopher Linington, Damo Xu, Miodrag L. Lukić, Foo Y. Liew,

Immune Cell Function and Interaction

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.