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)-alpha. Their numbers increased during active uveitis and scleritis and decreased following treatment. IL-17 was elevated in EAU and upregulated tumor necrosis factor (TNF)- a 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-gamma 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-gamma 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-gamma and/ or IL- 27 could be used for the treatment of chronic inflammation.