Suppressors of Cytokine Signalling (SOCS) have Neuroprotective Roles in Retina

National Eye Institute

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Abstract

We found that decrease of SOCS3 in mice with STAT3 deficiency in B cells exacerbates uveitis by promoting expansion of pathogenic lymphocytes. Surprisingly, CD4-IRF4KO mice are resistant to EAU, antagonized pathogenic TH17 responses and induced expansion of lymphocytes that secrete IL-10 and IL-35 in eye and lymphoid tissues. Loss of irf4 also correlated with defective T-cell metabolism and expression of Ikaros zinc-finger transcription factors required for lymphocyte differentiation, metabolism and cell-fate decisions. Our study thus suggests that synergistic effects of IRF4 and IkZFs induce metabolic reprogramming of differentiating lymphocytes and may thereby regulate immunity during uveitis by controlling the relative abundance of T and B lymphocyte subsets during inflammation. Our data also suggest that IRF4 and IRF8 have diametrically opposite effects in T cells with IRF4 activating proinflammatory responses while IRF8 promotes immune suppression.