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Wai Po Chong, Reiko Horai, Phyllis Silver, Yingyos Jittayasothorn, Chi-Chao Chan, Rachel R Caspi; IL-17A is dispensable for spontaneous autoimmune uveitis and negatively regulates the Th17 cytokine program. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© 2017 Association for Research in Vision and Ophthalmology.
The Th17 response has been associated with host defense as well as with autoimmune diseases in patients and in experimental animal models. Th17 cells cause tissue damage by producing a stereotypic profile of pro-inflammatory cytokines, including Interleukin (IL)-17A, IL-17F, Granulocyte macrophage colony-stimulating factor (GM-CSF) and IL-22. IL-17A is recognized as the Th17 signature cytokine and IL-17-producing T cells are pathogenic effectors in models of autoimmunity, including experimental autoimmune uveitis induced by immunization with the retinal protein IRBP in complete Freund’s adjuvant. Paradoxically, however, injection of exogenous IL-17 was shown to ameliorate the disease (Ke et al., JI 2009).
Using a recently developed model of spontaneous uveitis in R161H mice, which express a transgenic T cell receptor specific for IRBP, we investigated the susceptibility to disease on an IL-17A deficient background. Additionally, IRBP-specific T cells from IL17A sufficient and deficient R161H mice were polarized under Th17 conditions and were adoptively transferred to WT recipient to investigate their cytokine profile and their ability to induce uveitis.
We found that IL-17A deficiency did not reduce the severity of uveitis in R161H mice. Furthermore, IL-17A deficient R161H T cells polarized under Th17 conditions and adoptively transferred into wild type recipients induced similar disease to IL-17A sufficient R161H T cells. Interestingly, IL-17A deficient R161H T cells polarized under Th17 conditions produced elevated amounts of other Th17-related cytokines, i.e. IL-17F, GM-CSF and IL-22. Conversely, supplementing Th17 polarization cultures of IL-17A deficient T cells with recombinant IL-17A, reduced the elevated production of those cytokines.
These data suggest that: (a) IL-17A itself is not necessary for the pathogenicity of uveitogenic Th17 cells in this model, and (b) that IL-17A exerts feedback inhibition on Th17 cells to control their expression of other Th17-related cytokines.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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