The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling

被引：415

作者：

Carty, Michael

Goodbody, Rory

Schroeder, Martina

Stack, Julianne

Moynagh, Paul N.

Bowie, Andrew G. ^{[1
]}

机构：

[1] Univ Dublin Trinity Coll, Sch Biochem & Immunol, Dublin 2, Ireland

[2] Natl Univ Ireland Univ Coll Dublin, Conway Inst, Sch Biomol & Biomed Sci, Dublin 4, Ireland

来源：

NATURE IMMUNOLOGY | 2006年 / 7卷 / 10期

关键词：

D O I：

10.1038/ni1382

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

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页码：1074 / 1081

页数：8

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