Constitutive expression of IL-27 in neuro-retina negatively regulates THIL-17 cell development (95.25)

Abstract

Abstract Ocular immune privilege is maintained by constitutive expression of inhibitory molecules such as TGF-b, FAS and FAS-ligand. Here, we describe a model of immune privilege for the eye based on IL-27-induced suppression of Th17 responses. We show that Th17 cells are elevated in retina of mice during experimental autoimmune uveoretinitis (EAU) and treatment with anti-IL17 Abs reduces EAU severity. It is of note that the increase and subsequent trafficking of Th17 cells into the retina during EAU is accompanied by corresponding increases in IL-27 and IFN? in the retina. We further show that IL-27 is constitutively expressed in human or mouse retina and that IFN? upregulates its expression in retinal cells. Of particular interest is inhibition of the proliferation of uveitogenic Th17 cells by IL-27, suggesting that IFN? may mitigate uveitis by antagonizing Th17 expansion through induction of IL-27 in the target tissue. In a co-culture system the expansion of Th17 cells (propagated under Th17 polarizing conditions) is inhibited by primary retina cells. However, addition of anti-IL-27 antibody into the culture overrides the inhibitory effects of the retinal cells on the expansion of Th17 cells. The data presented suggests that inhibitory effects on inflammatory cells by the retina are mediated in part by endogenously produced IL-27 and establishes mechanistic links between IL-27 expression and anti- Th17 effects in the eye.