IL-33 attenuates the development of experimental autoimmune uveitis

Mark Barbour, Debbie Allan, Heping Xu, Cheng Pei, Mei Chen, Wanda Niedbala, Sandra Y. Fukada, Anne-Galle Besnard, Jose C. Alves-Filho, Xiaoguang Tong, John V. Forrester, Foo Yew Liew, Hui-Rong Jiang

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Abstract

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.

Original languageEnglish
Pages (from-to)3320-3329
Number of pages10
JournalEuropean Journal of Immunology
Volume44
Issue number11
Early online date12 Aug 2014
DOIs
Publication statusPublished - 30 Nov 2014

Keywords

  • animals
  • autoimmune diseases
  • CD4-positive T-lymphocytes
  • cultured cells
  • coculture techniques
  • disease models, animal
  • eye
  • eye proteins
  • inflammation
  • interferon-gamma
  • interleukin-17
  • interleukin-4
  • interleukin-5
  • interleukins
  • macrophages
  • mice
  • mice, inbred BALB C
  • mice, inbred C57BL
  • mice, knockout
  • RNA, messenger
  • interleukin receptors
  • retinal pigment epithelium
  • uveitis

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