Carty Michael, Goodbody Rory, Schröder Martina, Stack Julianne, Moynagh Paul N, Bowie Andrew G
School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland.
Nat Immunol. 2006 Oct;7(10):1074-81. doi: 10.1038/ni1382. Epub 2006 Sep 10.
Toll-like receptors discriminate between different pathogen-associated molecules and activate signaling cascades that lead to immune responses. The specificity of Toll-like receptor signaling occurs by means of adaptor proteins containing Toll-interleukin 1 receptor (TIR) domains. Activating functions have been assigned to four TIR adaptors: MyD88, Mal, TRIF and TRAM. Here we characterize a fifth TIR adaptor, SARM, as a negative regulator of TRIF-dependent Toll-like receptor signaling. Expression of SARM blocked gene induction 'downstream' of TRIF but not of MyD88. SARM associated with TRIF, and 'knockdown' of endogenous SARM expression by interfering RNA led to enhanced TRIF-dependent cytokine and chemokine induction. Thus, the fifth mammalian TIR adaptor SARM is a negative regulator of Toll-like receptor signaling.
Toll样受体能够区分不同的病原体相关分子，并激活导致免疫反应的信号级联反应。Toll样受体信号传导的特异性通过含有Toll-白细胞介素1受体（TIR）结构域的衔接蛋白来实现。已经确定有四种TIR衔接蛋白具有激活功能：MyD88、Mal、TRIF和TRAM。在这里，我们将第五种TIR衔接蛋白SARM鉴定为TRIF依赖性Toll样受体信号传导的负调节因子。SARM的表达阻断了TRIF下游的基因诱导，但不影响MyD88下游的基因诱导。SARM与TRIF相互作用，通过干扰RNA对内源性SARM表达进行“敲低”导致TRIF依赖性细胞因子和趋化因子的诱导增强。因此，第五种哺乳动物TIR衔接蛋白SARM是Toll样受体信号传导的负调节因子。
