Socs1 Inhibits Experimental Autoimmune Uveitis by Limiting Expansion of Th17 and Th1 Cells in the Retina

Abstract

Purpose: : Suppressor of cytokine signaling 1 (SOCS1) regulates the intensity and duration of the activities of pro-inflammatory cytokines. In this study we have investigated whether targeted over-expression of SOCS1 in the retina can prevent or mitigate uveitis.

Methods: : We have generated and characterized transgenic mice with targeted over-expression of SOCS1 in the retina under direction of the mouse opsin-promoter. We induced experimental autoimmune uveitis (EAU) in wild type (WT) and SOCS1 transgenic (SOCS1-TR) mice by immunization with interphotoreceptor retinoid binding protein (IRBP) in CFA. EAU development and disease severity was assessed by fundoscopy and histopathology. Phenotype of lymphocytes in the blood, lymph nodes and retina was characterized by FACS and intracellular cytokine staining assay. IRBP-specific T cells were adoptively transferred into SOCS1-TR mice to further characterize protective role of SOCS1 in the retina.

Results: : We show a 5-fold decrease in lymphocytes infiltrating the retina of SOCS1-TR and this coincided with substantial reduction of EAU in SOCS1-TR compared to WT mice. We confirmed these findings by showing that fewer numbers of the transferred IRBP-specific T cells entered the retina of SOCS1-TR and induced less severe disease compared to adoptively transferred EAU in WT mice.

Conclusions: : Our results suggest that SOCS1 may function as a neuroprotective protein that mitigates deleterious effects of proinflammatory cytokines produced in the retina during intraocular inflammation. Thus, targeted delivery of SOCS1 into retinal cells may be beneficial in control inflammatory retinal disease.

Keywords: uveitis-clinical/animal model • immunomodulation/immunoregulation • autoimmune disease