Forced expression of suppressor of cytokine signaling 3 in T cells protects the development of concanavalin A-induced hepatitis in mice
Forced expression of suppressor of cytokine signaling 3 in T cells protects the development of concanavalin A-induced hepatitis in mice
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DOI：
10.1016/j.clim.2009.08.015
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发表时间：
2009-12-01
影响因子：
8.6
通讯作者：
Matsukawa, Akihiro
中科院分区：
文献类型：
--
作者：
Fushimi, Soichiro;Ogino, Tetsuya;Matsukawa, Akihiro
T细胞在肝病中起中心作用，但细胞因子信号转导的调节机制尚不清楚。在本研究中，我们探讨了T细胞中SOCS3在刀豆蛋白A(ConA)诱导的肝炎中的作用。与对照组相比，T细胞特异性过表达SOCS3(SOCS3-CTG)的小鼠肝损伤减轻，小鼠存活率提高，这一事件与凋亡信号Fas和pStat1减少有关。SCCS3-CTG肝组织中Th1细胞因子/趋化因子表达降低，Th1转录因子T-bet表达降低。肝淋巴细胞流式细胞仪分析显示，活化的CD4(+)T细胞、细胞毒性T细胞和。SOCS3-CTG肝组织中自然杀伤T细胞明显减少，肝细胞损伤损伤分子穿孔素和颗粒酶8表达减少。这些结果表明，SOCS3在T细胞中的强制表达通过抑制Th1反应的多个阶段来预防ConA诱导的肝损伤。(C)2009 Elsevier Inc.保留所有权利。
T cells play central rotes in liver diseases, but the regulatory mechanism by cytokine signaling is not well understood. In the present study, we explored the role of SOCS3 in T cells in concanavalin A (ConA)-induced hepatitis. Mice with T-cell-specific overexpression of SOCS3 (SOCS3-cTg) showed reduced hepatic damage and improved mice survival relative to the control, an event that was associated with decreased apoptotic signals Fas and pStat1. Expression of Th1-cytokines/chemokines was decreased in SCCS3-cTg liver with reduced expression of T-bet, a Th1-transcription factor. Flow cytometric analysis of the liver lymphocytes demonstrated that activated CD4(+) T cells, cytotoxic T cells and. natural killer T cells were significantly decreased in SOCS3-cTg liver with decreased expression of perforin and granzyme 8, injurious molecules for hepatocyte damage. These results suggest that forced expression of SOCS3 in T cells prevents ConA-induced liver injury by inhibiting several phases of Th1 responses. (C) 2009 Elsevier Inc. All rights reserved.