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ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance

机译:ST2是白介素1受体和Toll样受体4信号转导的抑制剂,并维持内毒素耐受性

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摘要

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-B, leading to the production of proinflammatory cytokines. ST2 is a member of the TIR family that does not activate NF-kB and has been suggested as an important effector molecule of T helper type 2 (T_H2) 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_H2 responses, as inhibition of TLRs promotes a T_H2 response, and also identify ST2 as a key regulator of endotoxin tolerance.
机译:Toll-白介素1受体(TIR)超家族(定义为细胞内TIR结构域的存在)通过激活转录因子NF-B来启动先天免疫,从而导致促炎性细胞因子的产生。 ST2是不激活NF-kB的TIR家族的成员,已被建议作为2型T辅助细胞(T_H2)反应的重要效应分子。我们在这里显示ST2的膜结合形式通过隔离适配器MyD88和Mal负调节I型白介素1受体(IL-1RI)和Toll样受体4(TLR4),但TLR3信号却不起作用。与野生型小鼠相反,ST2缺陷型小鼠未能产生内毒素耐受性。因此,这些结果为ST2在T_H2反应中的功能提供了分子解释,因为TLR的抑制促进了T_H2反应,并且还确定ST2是内毒素耐受性的关键调节剂。

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