Article abstract
Nature Medicine 13, 711 - 718 (2007)
Published online: 13 May 2007 | doi:10.1038/nm1585
TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1
Ahjoku Amadi-Obi1,4, Cheng-Rong Yu1,4, Xuebin Liu1, Rashid M Mahdi1, Grace Levy Clarke2, Robert B Nussenblatt2, Igal Gery3, Yun Sang Lee1 & Charles E Egwuagu1
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)-
. Their numbers increased during active uveitis and scleritis and decreased following treatment. IL-17 was elevated in EAU and upregulated tumor necrosis factor (TNF)-
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- and inhibited proliferation of TH17. These findings suggest that TH1 cells may mitigate uveitis by antagonizing the TH17 phenotype through the IFN-–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- and/or IL-27 could be used for the treatment of chronic inflammation.
- Molecular Immunology Section, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
- Clinical Immunology Section, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
- Experimental Immunology Section, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
- These authors contributed equally to this work.
Correspondence to: Charles E Egwuagu1 e-mail: egwuaguc@nei.nih.gov
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