TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1

T-helper type 17 cells (T H 17) are implicated in rodent models of immune-mediated diseases. Here we report their involvement in human uveitis and scleritis, and validate our findings in experimental autoimmune uveoretinitis (EAU), a model of uveitis. T H 17 cells were present in human peripheral blood mononuclear cells (PBMC), and were expanded by interleukin (IL)-2 and inhibited by interferon (IFN)-γ. Their numbers increased during active uveitis and scleritis and decreased following treatment. IL-17 was elevated in EAU and upregulated tumor necrosis factor (TNF)-α in retinal cells, suggesting a mechanism by which T H 17 may contribute to ocular pathology. Furthermore, IL-27 was constitutively expressed in retinal ganglion and photoreceptor cells, was upregulated by IFN-γ and inhibited proliferation of T H 17. These findings suggest that T H 1 cells may mitigate uveitis by antagonizing the T H 17 phenotype through the IFN-γ–mediated induction of IL-27 in target tissue. The finding that IL-2 promotes T H 17 expansion provides explanations for the efficacy of IL-2R antibody therapy in uveitis, and suggests that antagonism of T H 17 by IFN-γ and/or IL-27 could be used for the treatment of chronic inflammation.