SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling

被引：477

作者：

Wald, D

Qin, JZ

Zhao, ZD

Qian, YC

Naramura, M

Tian, LP

Towne, J

Sims, JE

Stark, GR

Li, XX

机构：

[1] Cleveland Clin Fdn, Dept Immunol, Cleveland, OH 44195 USA

[2] Amgen Corp, Seattle, WA 98101 USA

来源：

NATURE IMMUNOLOGY | 2003年 / 4卷 / 09期

关键词：

D O I：

10.1038/ni968

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The Toll-like receptor-interleukin 1 receptor signaling (TLR-IL-1R) receptor superfamily is important in differentially recognizing pathogen products and eliciting appropriate immune responses. These receptors alter gene expression, mainly through the activation of nuclear factor-kappaB and activating protein 1. SIGIRR (single immunoglobulin IL-1R-related molecule), a member of this family that does not activate these factors, instead negatively modulates immune responses. Inflammation is enhanced in SIGIRR-deficient mice, as shown by their enhanced chemokine induction after IL-1 injection and reduced threshold for lethal endotoxin challenge. Cells from SIGIRR-deficient mice showed enhanced activation in response to either IL-1 or certain Toll ligands. Finally, biochemical analysis indicated that SIGIRR binds to the TLR-IL-1R signaling components in a ligand-dependent way. Our data show that SIGIRR functions as a biologically important modulator of TLR-IL-1R signaling.

引用

页码：920 / 927

页数：8

共 36 条

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