Suppressor of Cytokine Signaling-1 Overexpression Protects Pancreatic β Cells from CD8+ T Cell-Mediated Autoimmune Destruction

摘要: In type 1 diabetes, cytokine action on β cells potentially contributes to cell destruction by direct cytotoxicity, inducing Fas expression, and up-regulating class I MHC chemokine expression increase immune recognition. To simultaneously block responsiveness multiple cytokines, we overexpressed suppressor of signaling-1 (SOCS-1). This completely prevented progression diabetes in CD8+ TCR transgenic nonobese diabetic (NOD) 8.3 mice without affecting pancreas infiltration partially nontransgenic NOD mice. SOCS-1 appeared protect at least part inhibiting TNF- IFN-γ-induced cells. was up-regulated vivo prediabetic NOD8.3 mice, this inhibited SOCS-1. Additionally, up-regulation IL-15 were SOCS-1, which correlated with suppressed T proliferation vitro. Despite this, priming unaffected. Therefore, blocking responses cytokines impairs recognition blocks mechanisms destruction, but does not prevent recruitment the islets. Our findings suggest that increasing may be useful as a strategy cell-mediated well more generally cytokine-dependent tissue inflammatory diseases.