A novel negative regulator for IL-1 receptor and Toll-like receptor 4

被引：31

作者：

Liew, FY ^{[1
]}

Liu, HY ^{[1
]}

Xu, D ^{[1
]}

机构：

[1] Univ Glasgow, Div Immunol Infect & Inflammat, Glasgow G11 6NT, Lanark, Scotland

来源：

IMMUNOLOGY LETTERS | 2005年 / 96卷 / 01期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

T1/ST2; IL-1R; toll-like receptors; endotoxin tolerance;

D O I：

10.1016/j.imlet.2004.07.008

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-IL-1 receptor (TIR) superfamily, defined by the presence of an intracellular TIR domain, initiates innate immunity via NF-KB activation, leading to production of proinflammatory cytokines. ST2 is a member of the TIR family that does not activate NT-KB and has been suggested as an important effector molecule of type 2 T helper cell responses. We have recently demonstrated that the membrane bound form of ST2 (ST2L) negatively regulated IL- 1RI and 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, ST2 suppresses IL- 1R and TLR4 signaling via MyD88 and Mal-dependent pathways and modulates innate immunity. The results provide a molecular explanation for the role of ST2 in T(H)2 responses since inhibition of TLRs will promote a T(H)2 response and also identify ST2 as a key regulator of endotoxin tolerance. (C) 2004 Elsevier B.V. All rights reserved.

引用

页码：27 / 31

页数：5

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