SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling
SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling
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DOI：
10.1038/ni968
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发表时间：
2003-09-01
影响因子：
30.5
通讯作者：
Li, XX
中科院分区：
文献类型：
--
作者：
Wald, D;Qin, JZ;Li, XX
Toll样受体-白细胞介素1受体信号转导（TLR-IL-1 R）受体超家族在差异识别病原体产物和引发适当的免疫应答中是重要的。这些受体改变基因表达，主要通过激活核因子-κ B和激活蛋白1。SIGIRR（单个免疫球蛋白IL-1 R相关分子）是该家族的成员，不激活这些因子，而是负调节免疫反应。炎症在SIGIRR缺陷型小鼠中增强，如通过它们在IL-1注射后增强的趋化因子诱导和降低的致死内毒素攻击阈值所示。来自SIGIRR缺陷型小鼠的细胞显示响应于IL-1或某些Toll配体的增强的活化。最后，生化分析表明SIGIRR以配体依赖性方式结合TLR-IL-1 R信号传导组分。我们的数据表明，SIGIRR作为TLR-IL-1 R信号传导的生物学重要调节剂发挥作用。
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.