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- Title
T<sub>H</sub>17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1.
- Authors
Amadi-Obi, Ahjoku; Cheng-Rong Yu; Xuebin Liu; Mahdi, Rashid M.; Clarke, Grace Levy; Nussenblatt, Robert B.; Gery, Igal; Yun Sang Lee; Egwuagu, Charles E.
- Abstract
T-helper type 17 cells (TH17) 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. TH17 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 TH17 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 TH17. These findings suggest that TH1 cells may mitigate uveitis by antagonizing the TH17 phenotype through the IFN-γ–mediated induction of IL-27 in target tissue. The finding that IL-2 promotes TH17 expansion provides explanations for the efficacy of IL-2R antibody therapy in uveitis, and suggests that antagonism of TH17 by IFN-γ and/or IL-27 could be used for the treatment of chronic inflammation.
- Publication
Nature Medicine, 2007, Vol 13, Issue 6, p711
- ISSN
1078-8956
- Publication type
Academic Journal
- DOI
10.1038/nm1585