The role of Fas in autoimmune diabetes
The role of Fas in autoimmune diabetes
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DOI：
10.1016/s0092-8674(00)80178-6
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发表时间：
1997-04-04
期刊：
影响因子：
64.5
通讯作者：
Matis, LA
中科院分区：
文献类型：
--
作者：
Chervonsky, AV;Wang, Y;Matis, LA
免疫特权部位表达Fas配体(FasL)，保护它们免受活化的T细胞的攻击，这些T细胞表达Fas并在与FasL接触时死亡。为了保护非肥胖糖尿病小鼠(NOD)免受自身免疫性糖尿病的影响，我们用β细胞特异性的大鼠胰岛素-1启动子获得了FasL转基因NOD小鼠。令人惊讶的是，这些转基因小鼠对糖尿病T细胞表现出高度的敏感性，这是由于T细胞介导的Fas诱导的β细胞的自我破坏。Fas阴性的NODlpr/LPR动物对糖尿病T细胞和自发性糖尿病具有抵抗力。因此，诱导β细胞上Fas的表达并随后破坏是自身免疫性糖尿病的主要发病机制。
Immunologically privileged sites express Fas ligand (FasL), which protects them from attack by activated T cells that express Fas and die upon contact with FasL. In an attempt to protect nonobese diabetic mice (NOD) from autoimmune diabetes, we made FasL transgenic NOD mice using the beta cell-specific rat insulin-1 promoter. Surprisingly, these transgenic mice showed heightened sensitivity to diabetogenic T cells, which was due to self-destruction of beta cells upon T cell-mediated induction of Fas. Fas-negative NODlpr/lpr animals were resistant to diabetogenic T cells and to spontaneous diabetes. Thus, induction of Fas expression on beta cells and their subsequent destruction constitutes the main pathogenic mechanism in autoimmune diabetes.