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H. Haruta, S. Hoki, H. Mashimo, K. Nakai, N. Ohguro, T. Naka; Interleukin-6 Blockade in CD4 T Cells Inhibits the Development of Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):819.
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© ARVO (1962-2015); The Authors (2016-present)
A novel subset of interleukin (IL)-17-producing CD4+ T helper cells (Th17) is thought to play a pivotal role in experimental autoimmune uveitis (EAU) and human uveitis. Recent studies also have indicated that IL-6 promotes Th17 differentiation in vitro and in vivo. The aim of this study is to investigate the role of IL-6 signaling in CD4 T cells in the development of EAU.
EAU was induced by immunization with interphotoreceptor retinoid binding protein (IRBP) in wild type (WT), IL-6 knockout (KO) mice and T cell-specific signal transducer activated signal transducers and activator of transcription 3 (STAT3) KO female mice, which are defective in IL-6 signaling. All experimental mice used were on the C57BL/6 background. The clinical scores of EAU and CD4 T cell differentiation in these mice were analyzed. All mice were treated according to the ARVO Statement on the Use of Animals in Ophthalmic and Vision Research.
EAU did not develop in IL-6KO and STAT3KO mice while WT mice displayed severe inflammation. Th17 cell differentiation in cervical lymph nodes on day 10 after immunization also decreased in IL-6KO and STAT3KO compared to WT mice. IRBP specific CD4+CD25+ T regulatory cells were observed to be significantly increased in IL-6KO mice.
This study showed that IL-6 and STAT3 in T cells are essential in the development of EAU and for the differentiation of highly pro-inflammatory Th17 cells. The protective effect of defective IL-6 signaling in the development of EAU is associated with the inhibition of differentiation of highly pro-inflammatory Th17 cells and an increase in the frequency of immunosuppressive T regulatory cells.
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