Autoimmune diabetes is blocked in Stat4-deficient mice

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• 作者：Yang ; Zandong ; Chen ; Meng ; Ellett ; Justin D. ; Fialkow ; Lawrence B. ; Carter ; Jeffrey D. ; McDuffie ; Marcia ; et. al.
• 关键词：Autoimmunity ; Diabetes ; IL-12 ; NOD mice ; STAT4
• 刊名：Journal of Autoimmunity
• 出版年：2004
• 出版时间：May, 2004
• 年：2004
• 卷：22
• 期：3
• 页码：191-200
• 全文大小：543 K

文摘

Signal transducers and activators of transcription (STAT) proteins are activated in response to many cytokines, growth factors and hormones. STAT4 mediates IL-12 signaling and regulates T helper 1 (Th1) cell differentiation. Both IL-12 and Th1 cell activation participate in the development of autoimmune diabetes. In this study, we investigated the role of STAT4 in autoimmune diabetes. We crossbred Stat4 deficient (Stat4^−/−) mice with nonobese diabetic (NOD) mice to generate the Stat4^−/−NOD model. In Stat4^−/−NOD mice, serum levels of both IFN-γ and IL-2 were significantly reduced as compared to the controls. Insulin secretion in pancreatic islets was preserved in Stat4^−/−NOD mice. Significantly, disruption of Stat4 activation completely prevented the development of spontaneous diabetes in NOD mice. This study reveals the important role of STAT4 in autoimmune diabetes pathogenesis.