Myeloid differentiation factor 88-dependent and -independent pathways in Toll-like receptor signaling
Myeloid differentiation factor 88-dependent and -independent pathways in Toll-like receptor signaling
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DOI：
10.1086/374749
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发表时间：
2003-06-15
影响因子：
6.4
通讯作者：
Hoshino, K
中科院分区：
文献类型：
--
作者：
Akira, S;Hoshino, K
Toll样受体（TLR）在检测体内入侵病原体中发挥重要作用。单个TLR识别来自病原体的不同组分，随后产生细胞因子。TLR家族含有细胞外富含亮氨酸的重复结构域和与白细胞介素（IL）-1受体（IL-1 R）家族同源的胞质结构域。刺激后，TLR通过衔接髓样分化因子88（MyD 88）募集IL-1 R相关激酶，并诱导NF-κ B和丝裂原活化蛋白激酶的活化。在MyD 88缺陷型细胞中，响应于每个TLR配体的细胞因子产生被完全消除，这表明MyD 88是IL-1 R/Toll家族中必需的共享信号分子。TLR 4信号具有MyD 88非依赖性途径，其参与通过IFN调节因子-3活化诱导I型干扰素（IFN）和IFN诱导型基因。最近发现的一种衔接分子，即含有Toll-IL受体结构域的衔接蛋白/MyD 88衔接子样分子，可能参与MyD 88非依赖性途径。
Toll-like receptors (TLRs) play an essential role in the detection of invading pathogens in the body. Individual TLRs recognize distinct components derived from pathogens, which is followed by cytokine production. The TLR family harbors extracellular leucine-rich repeat domains and a cytoplasmic domain that is homologous to that of the interleukin (IL)-1 receptor (IL-1R) family. After stimulation, TLR recruits IL-1R-associated kinase via adaptor myeloid differentiation factor 88 (MyD88) and induces activation of NF-kappaB and mitogen-activated protein kinases. Cytokine production in response to each TLR ligand is completely abrogated in MyD88-deficient cells, which indicates that MyD88 is an essential shared signaling molecule in the IL-1R/Toll family. The TLR4 signal has an MyD88-independent pathway that is involved in induction of type I interferons (IFNs) and IFN-inducible genes via IFN regulatory factor-3 activation. A recently identified adaptor molecule, Toll-IL receptor domain-containing adaptor protein/MyD88 adaptor-like, may participate in the MyD88-independent pathway.