A critical role for stat3 signaling in immune tolerance
A critical role for stat3 signaling in immune tolerance
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DOI：
10.1016/s1074-7613(03)00232-2
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发表时间：
2003-09-01
期刊：
影响因子：
32.4
通讯作者：
Sotomayor, EM
中科院分区：
文献类型：
--
作者：
Cheng, FD;Wang, HW;Sotomayor, EM
抗原呈递细胞（APC）可以诱导T细胞活化以及T细胞耐受。APC调节免疫系统的这一关键决定的分子机制还不清楚。在这里，我们表明，Stat 3信号在抗原特异性T细胞耐受的诱导中起着关键作用。靶向破坏APC中的Stat 3信号传导导致抗原特异性CD 4（+）T细胞对体内致耐受性刺激的应答。此外，缺乏Stat 3的APC在体外有效地打破抗原特异性T细胞无能。相反，APC中Stat 3活性的增加会导致抗原特异性T细胞反应受损。因此，Stat 3信号提供了一种新的分子靶点，用于操纵免疫激活/耐受，这是一个在自身免疫、移植和癌症免疫治疗中具有深远意义的核心决定。
Antigen-presenting cells (APCs) can induce T cell activation as well as T cell tolerance. The molecular mechanisms by which APCs regulate this critical decision of the immune system are not well understood. Here we show that Stat3 signaling plays a critical role in the induction of antigen-specific T cell tolerance. Targeted disruption of Stat3 signaling in APCs resulted in priming of antigen-specific CD4(+) T cells in response to an otherwise tolerogenic stimulus in vivo. Furthermore, APCs devoid of Stat3 effectively break antigen-specific T cell anergy in vitro. Conversely, increased Stat3 activity in APCs led to impaired antigen-specific T cell responses. Stat3 signaling provides, therefore, a novel molecular target for manipulation of immune activation/tolerance, a central decision with profound implications in autoimmunity, transplantation, and cancer immunotherapy.