ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance
ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance
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DOI：
10.1038/ni1050
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发表时间：
2004-04-01
影响因子：
30.5
通讯作者：
Liew, FY
中科院分区：
文献类型：
--
作者：
Brint, EK;Xu, DM;Liew, FY
Toll-白细胞介素1受体（TIR）超家族由细胞内TIR结构域的存在定义，通过激活转录因子NF-κ B启动先天免疫，导致促炎细胞因子的产生。ST 2是TIR家族的成员，其不激活NF-κ B，并且已被认为是T辅助2型（T（H）2）应答的重要效应分子。我们在这里表明，膜结合形式的ST 2负调节I型白细胞介素1受体（IL-1 RI）和Toll样受体4（TLR 4），但不TLR 3信号通过螯合的衔接子MyD 88和Mal。与野生型小鼠相比，ST 2缺陷小鼠未能开发内毒素耐受性。因此，这些结果为ST 2在T（H）2应答中的功能提供了分子解释，因为TLR的抑制促进了T（H）2应答，并且还鉴定了ST 2作为内毒素耐受性的关键调节剂。
The Toll-interleukin 1 receptor (TIR) superfamily, defined by the presence of an intracellular TIR domain, initiates innate immunity through activation of the transcription factor NF-kappaB, leading to the production of proinflammatory cytokines. ST2 is a member of the TIR family that does not activate NF-kappaB and has been suggested as an important effector molecule of T helper type 2 (T(H)2) responses. We show here that the membrane-bound form of ST2 negatively regulated type I interleukin 1 receptor (IL-1RI) and Toll-like receptor 4 (TLR4) but not TLR3 signaling by sequestrating the adaptors MyD88 and Mal. In contrast to wild-type mice, ST2-deficient mice failed to develop endotoxin tolerance. Thus, these results provide a molecular explanation for the function of ST2 in T(H)2 responses, as inhibition of TLRs promotes a T(H)2 response, and also identify ST2 as a key regulator of endotoxin tolerance.