Role of IL-12 family cytokines in human autoimmune Uveitis

National Eye Institute

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Abstract

We generated IL-35 reporter mouse (IL-35/YFP-knock-in or p35-KI) and demonstrate that photoreceptor neurons constitutively secrete IL-35 which might protect retina from persistent low-grade inflammation that can impair photoreceptor functions. Furthermore, the p35-KI mouse which is hemizygous at il12a locus develops more severe uveitis because of reduced IL-35 expression. Interestingly, onset and exacerbation of uveitis in p35-KI mice caused by extravasation of proinflammatory Th1/Th17 lymphocytes into the retina was preceded by dramatic decrease of IL-35 attributable to massive death of photoreceptor cells. Thus, while inflammation-induced death of photoreceptors and loss of protective effects of IL-35 exacerbated uveitis, our data also suggest that constitutive production of IL-35 in retina might have housekeeping functions that promote sterilization immunity in the neuroretina and maintain ocular immune privilege.