The Distinct Role of IFN- and IL-17 on Experimental Autoimmune Uveitis

Abstract

Purpose:: In experimental autoimmune uveoretinitis (EAU), a model of human autoimmune uveitis, activated T cells and macrophages move into the retina and cause tissue damage. A novel CD4⁺ subset distinct from Th1 and Th2 cells, termed Th17, has recently been described. Th17 cells produce IL-17, which exerts strong proinflammatory activities and autoimmune reaction. Although EAU have been traditionally classified as Th1-mediated disease involving IFN-γ production, in this study we analyzed the possible involvement of Th17 in EAU.

Methods:: Mice (either wild-type or IL-17-deficient) were immunized with interphotoreceptor retinoid-binding protein peptide 1-20 in CFA with M. tuberculosis H37RA plus pertussis toxin; the course of EAU in IL-17KO mice, and effects of subretinal transfer of antigen-specific Th17 cells on the course of EAU were examined. Severity of EAU was evaluated clinically and histopathologically. Cytokine/chemokine expression in the eye and lymph node cells were examined by ELISA and RT-PCR methods.

Results:: IL-17-deficient mice showed early recovery from EAU compared to WT mice. At later phases, IFN-γ production in the eyes of IL-17-deficient mice or in lymph node cells is the same as that in WT mice. Subretinal transfer of in vitro-differentiated IRBP-specific Th17 cells induced EAU.

Conclusions:: In addition to the previously reported roles of Th1 cells, IL-17⁺ T cells may also contribute to the development of EAU, especially at chronic phases of inflammation. Both Th1 and Th17 responses may drive pathogenesis of experimental autoimmune uveitis, and thus IL-17 also may be a target for therapy.

Keywords: uveitis-clinical/animal model