WDFY1 mediates TLR3/4 signaling by recruiting TRIF
WDFY1 mediates TLR3/4 signaling by recruiting TRIF
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WDFY1 通过招募 TRIF 介导 TLR3/4 信号传导
DOI：
10.15252/embr.201439637
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发表时间：
2015-04-01
期刊：
影响因子：
7.7
通讯作者：
Liu, Yu
中科院分区：
文献类型：
--
作者：
Hu, Yun-Hong;Zhang, Yu;Liu, Yu
Toll样受体(Toll-like Receptor，TLRs)是一种模式识别受体，可以感知多种病原体，启动先天免疫反应，指导适应性免疫。除TLR3外，所有的TLRs都招募接头MyD88来最终诱导炎症基因的表达，而TLR3和内化的TLR4使用含有TIR结构域的接头TRIF来诱导型干扰素和炎症细胞因子。在这里，我们发现WD重复和含有FYVE结构域的蛋白WDFY1是TLR3/4信号通路中一个重要的适配蛋白。WDFY1的过表达增强了TLR3和TLR4介导的核因子-kappa B、干扰素调节因子3(IRF3)的激活，以及I型干扰素和炎性细胞因子的产生。WDFY1耗尽具有相反的效果。WDFY1与TLR3和TLR4相互作用，并介导TRIF向这些受体募集。我们的发现表明WDFY1在TLR-TRIF相互作用中起着关键作用，而TLR是TLR信号转导所必需的。
Toll-like receptors (TLRs) are pattern recognition receptors that sense a variety of pathogens, initiate innate immune responses, and direct adaptive immunity. All TLRs except TLR3 recruit the adaptor MyD88 to ultimately elicit inflammatory gene expression, whereas TLR3 and internalized TLR4 use TIR-domain-containing adaptor TRIF for the induction of type I interferon and inflammatory cytokines. Here, we identify the WD repeat and FYVE-domain-containing protein WDFY1 as a crucial adaptor protein in the TLR3/4 signaling pathway. Overexpression of WDFY1 potentiates TLR3-and TLR4-mediated activation of NF-kappa B, interferon regulatory factor 3 (IRF3), and production of type I interferons and inflammatory cytokines. WDFY1 depletion has the opposite effect. WDFY1 interacts with TLR3 and TLR4 and mediates the recruitment of TRIF to these receptors. Our findings suggest a crucial role for WDFY1 in bridging the TLR-TRIF interaction, which is necessary for TLR signaling.