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

Jiang, H.-R. et al. (2012) IL-33 attenuates EAE by suppressing IL-17 and IFN-γ production and inducing alternatively activated macrophages. European Journal of Immunology, 42(7), pp. 1804-1814. (doi: 10.1002/eji.201141947)

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Publisher's URL: http://dx.doi.org/10.1002/eji.201141947

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Prof Foo and Xu, Dr Damo and Besnard, Dr Anne-Gaelle and Niedbala, Dr Wanda and Alves-Filho, Dr Jose and Fukada, Dr Sandra and Linington, Professor Christopher and Jiang, Mr He and Goodyear, Professor Carl
Authors: Jiang, H.-R., Milovanović, M., Allan, D., Niedbala, W., Besnard, A.-G., Fukada, S. Y., Alves-Filho, J. C., Togbe, D., Goodyear, C. S., Linington, C., Xu, D., Lukic, M. L., and Liew, F. Y.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:European Journal of Immunology
Journal Abbr.:Eur. J. Immunol.
Publisher:Wiley-VCH Verlag
ISSN:0014-2980
ISSN (Online):1521-4141
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
445191The role of the 1L-33 in the innate and adaptive immune responses in asthmaGrace MurphyMedical Research Council (MRC)G0601422III -IMMUNOLOGY