More roles of IL-4 than being as an antagonist of IFN-γ in experimental autoimmune uveitis

Abstract

Abstract IL-4 appears to be beneficial for some autoimmune diseases. Despite its role in antagonizing pathogenic Th1 response, our recent work has demonstrated IL-4 possesses functions affecting the regulatory T (Treg) cells. Here we aimed to identify the role of IL-4 in the development of experimental autoimmune uveitis (EAU). EAU was induced in WT and IL-4 KO mice via active interphotoreceptor retinoid binding protein (IRBP) immunization, and the disease development was monitored by funduscopic and histology analysis as well as the IRBP-specific immune responses by flow cytometric analysis and ELISA. It showed that the onset of disease, if the clinical score equals to 1, was day 14 and 20 in IL-4KO and WT mice, respectively. The fundoscopic images demonstrated the more and bigger size of lesions, increased leukocyte infiltration, vasculitis and neovascularization in IL-4KO mice. The histological analysis also confirmed the mononuclear cell infiltration. Moreover, Th1 effector is known as the dominant pathogenic mediators, whereas Treg cells play an important and indispensable role in control of EAU progression and disease remission. The splenic T cells from IL-4 KO EAU animals produced significantly elevated level of IFN-γ in responding to IRBP stimulation. However, there seems no significant but some alternation in the presence of Treg cells (Foxp3+) among CD4+CD25+ T cells in the spleens and lymph nodes of IL-4 KO and WT mice. These results demonstrate the lack of IL-4 disrupting the induction of EAU and leading to an increased disease severity through not only antagonizing IFN-γ but also involved mechanisms of immune-regulation. Therefore, IL-4 might play more roles than being just an antagonist of IFN-γ in autoimmune uveitis.