Uveitis is mediated by activated CD4+ T cells that infiltrate the eye and the immunopathogenic process results from effects of pro-inflammatory cytokines elaborated predominantly, by T-helper type 1 (Th1) cells. Inhibition of the activities of pro-inflammatory cytokines is therefore a therapeutic goal in the treatment of inflammatory ocular diseases. Suppressors of cytokine signaling (SOCS) are a family of endogenous feedback regulators of cytokine activities. Members of the SOCS family are involved in the pathogenesis of many inflammatory diseases and we have previously shown that SOCS-3 is predominantly expressed in Th2 lymphocytes while SOCS1 is expressed at higher levels by Th1 cells. It was subsequently shown by others that SOCS5 is also expressed at high levels in Th1 cells. Together these studies established that SOCS3 is Th2 lineage marker while SOCS1 and SOCS5 are markers of the Th1 phenotype. In this project we have investigated the feasibility of using the level of SOCS expression in peripheral blood T cells as a diagnostic tool to monitor the intensity of inflammation in uveitis patients and to assess the response to humanized anti-Tac (HAT) therapy. The HAT antibody targets IL-2 receptor of Th1 and Th2 cells and therefore reduces the number of inflammatory T cells in the eye. As uveitis is characterized by infiltration of Th1 cells into the retina we investigated whether SOCS5 expression can serve as a surrogate marker of the level of T cells in the eye. Compared to healthy volunteers, the level of SOCS5 expression in peripheral blood T cells of uveitis patients is significantly elevated reflecting the role of Th1 cells in the etiology of human uveitis. On the other hand, comparison of SOCS levels before and after therapy reveals significant decrease in the level of SOCS5, suggesting that SOCS5 mRNA levels can be used as a diagnostic tool to monitor the response of uveitis patients to therapy. These results indicate that SOCS5 maybe involved in the etiology of uveitis and may serve as a new therapeutic target for the development of anti-uveitic drugs.
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