Involvement of SOCS Proteins in the Inhibitory Effect of IL-27 on Th17 Development (47.21)

Abstract

Abstract Suppressor Of Cytokine Signaling (SOCS) proteins are critical feedback inhibitors of the JAK/STAT signaling pathway and have neuroprotective effects. Recently, several reports have shown that the cytokine IL-27 functions as an inhibitory regulator, and represses the development of Th17 cells associated with autoimmune brain inflammation. Stimulation with IL-27 results in the activation of members of the STAT family, predominantly STAT-1 and STAT-3. In this study, we describe that IL-27 induces SOCS-1 and SOCS-3 gene expression, which is correlated with IL-27 induced STAT-1α and STAT-3 activation in anti-CD3 and anti-CD28 activated CD4+ T cells. Furthermore, we demonstrate that IL-27 induction of SOCS-1 and SOCS-3 gene expression in CD4+ T cells occurs at the transcriptional level as assessed by promoter assays. IL-27-induced SOCS-1 and SOCS-3 expression in CD4+ T cells from WT and STAT-1 deficient mice indicate that induction of SOCS-1 occurs in a STAT-1 dependent manner, and SOCS-3 induction partially depends on STAT-1. The inhibitory effects of IL-27 on Th17 development in CD4+ T cells with specific SOCS-3 deficiency and/or SOCS-1 knockdown will be investigated in the near future. These results indicate that IL-27 induces SOCS-1 and SOCS-3 expression in CD4+ T cells by activation of STAT-1α and/or STAT-3. We propose that SOCS-1 and SOCS-3 may participate in IL-27-mediated suppression of Th17 cell production and autoimmune brain inflammation.