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

Abstract:

: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)-gamma. Their numbers increased during active uveitis and scleritis and decreased following treatment. IL-17 was elevated in EAU and upregulated tumor necrosis factor (TNF)-alpha 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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Amadi-Obi A,Yu CR,Liu X,Mahdi RM,Clarke GL,Nussenblatt RB,Gery I,Lee YS,Egwuagu CE

doi

10.1038/nm1585

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

711-8

issue

6

eissn

1078-8956

issn

1546-170X

pii

nm1585

journal_volume

13

pub_type

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