SHP limits TLR signaling, an inducible transcriptional corepressor  

作　　者：Jiyan Zhang Beifen Shen 

机构地区：[1]Department of Molecular Immunology,Institute of Basic Medical Sciences,Beijing,China

出　　处：《Cellular & Molecular Immunology》2011年第6期445-446,共2页中国免疫学杂志（英文版）

摘　　要：Toll-like receptor(TLR)signaling stimulated by diverse microbial components plays a pivotal role in innate immunity by eliciting a powerful proinflammatory response that is essential for pathogen elimination.However,uncontrolled inflammation can result in tissue damage.Thus,TLR signaling has to be tightly controlled to maintain immune balance in the organism.The paradigm for modulating TLR signaling seems to center on the canonical nuclear factor-kB(NF-kB)pathway,most likely because of the central role of NF-kB in the production of various proinflammatory cytokines.1 In a recent issue of Nature Immunology,Yuk et al.have reported the identification of a novel endogenous NF-kB inhibitor in TLR signaling—small heterodimer partner(SHP)2 Interestingly,SHP functions in a self-regulating system:TLR signaling induces the expression of SHP in macrophages through Ca21-dependent activation of AMP-activated protein kinase(AMPK),which has anti-inflammatory effects3 SHP in turn decreases the expression of proinflammatory cytokines such as tumor necrosis factor-a(TNF-a)by physically binding to two key components of the canonical NF-kB pathway,namely,RelA/p65 and TNF receptorassociated factor 6(TRAF6)This work demonstrates an essential role for SHP in the negative control of TLR signaling and provides a novel underlying molecular mechanism.

关 键 词：immunity endogenous MAINTAIN 

分 类 号：R73[医药卫生—肿瘤]