IL-33 attenuates the development of experimental autoimmune uveitis

Barbour, M. et al. (2014) IL-33 attenuates the development of experimental autoimmune uveitis. European Journal of Immunology, 44(11), pp. 3320-3329. (doi: 10.1002/eji.201444671) (PMID:25116404) (PMCID:PMC4449115)

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Interleukin-33 (IL-33) is associated with several important immune-mediated disorders. However, its role in uveitis, an important eye inflammatory disease, is unknown. Here, we investigated the function of IL-33 in the development of experimental autoimmune uveitis (EAU). IL-33 and IL-33 receptor (ST2) were expressed in murine retinal pigment epithelial (RPE) cells in culture, and IL-33 increased the expression of Il33 and Mcp1 mRNA in RPE cells. In situ, IL-33 was highly expressed in the inner nuclear cells of the retina of naïve mice, and its expression was elevated in EAU mice. ST2-deficient mice developed exacerbated EAU compared with WT mice, and administration of IL-33 to WT mice significantly reduced EAU severity. The attenuated EAU in IL-33-treated mice was accompanied by decreased frequency of IFN-γ+ and IL-17+ CD4+ T cells and reduced IFN-γ and IL-17 production but with increased frequency of IL-5+ and IL-4+ CD4 T cells and IL-5 production in the draining lymph node and spleen. Macrophages from the IL-33-treated mice show a significantly higher polarization toward an alternatively activated macrophage phenotype. Our results therefore demonstrate that the endogenous IL-33/ST2 pathway plays an important role in EAU, and suggest that IL-33 represents a potential option for treatment of uveitis.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Liew, Prof Foo and Niedbala, Dr Wanda and Alves-Filho, Dr Jose and Fukada, Dr Sandra and Allan, Miss Debbie
Authors: Barbour, M., Allan, D., Xu, H., Pei, C., Chen, M., Niedbala, W., Fukada, S. Y., Besnard, A.-G., Alves-Filho, J. C., Tong, X., Forrester, J. V., Liew, F. Y., and Jiang, H.-R.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:European Journal of Immunology
ISSN (Online):1521-4141
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in European Journal of Immunology 44(11):3320-3329
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
431481The ST2 Receptor System in Health and DiseaseFoo LiewWellcome Trust (WELLCOME)080217/Z/06/ZIII -IMMUNOLOGY