Abstract
Purpose: :
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.
Methods: :
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.
Results: :
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.
Conclusions: :
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.
Keywords: autoimmune disease • inflammation • immunomodulation/immunoregulation