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 > School of Psychology & Neuroscience College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | European Journal of Immunology |
| Journal Abbr.: | Eur. J. Immunol. |
| Publisher: | Wiley-VCH Verlag |
| ISSN: | 0014-2980 |
| ISSN (Online): | 1521-4141 |
| Related URLs: |
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