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T. Yoshimura; WSX–1(IL–27R) Plays a Critical Role for the Initiation of Experimental Autoimmune Uveitis . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4540.
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© ARVO (1962-2015); The Authors (2016-present)
Experimental autoimmune uveoretinitis(EAU) is a model of human autoimmune uveitis where Th1 responses predominantly participate in the pathogenesis. WSX–1 is a novel class I cytokine receptor and is expressed in lymphoid tissues. Recent study revealed that WSX–1 is a subunit of IL–27 receptor, which plays a critical role in the initial development of Th1 responses. To delineate the in vivo role of WSX–1 in the induction of Th1–mediated autoimmune uveitis, we analyzed the course of EAU in WSX–1–deficient mice.
C57BL/6 mice and WSX–1–deficient mice were immunized with interphotoreceptor retinoid–binding protein peptide 1–20 in CFA with M.Tuberculosis H37RA and injected pertussis toxin. Severity of EAU was evaluated clinically and histopathologically. Cytokine and chemokine expression in the eye was examined by RT–PCR method.
WSX–1–deficient mice were protected from EAU development. WSX–1–deficient lymphocytes from immunized mice failed to produce IFN–γ as compared with wild–type lymphocytes. Expression of Th1–related chemokines, such as Rantes and IP–10, was suppressed in the eye of WSX–1–deficient mice relative to wild–type mice. As such, subretinal transfer of lymphocytes from immunized WSX–1–deficient mice did not induce EAU in the recipient mice.
IL–27/WSX–1(IL–27R) is critical for development of EAU and will be a target for therapy of autoimmune uveitis in human.
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