Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105
Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105
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DOI：
10.1038/ni1198
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发表时间：
2005-06-01
影响因子：
30.5
通讯作者：
Karp, CL
中科院分区：
文献类型：
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作者：
Divanovic, S;Trompette, A;Karp, CL
Toll样受体（TLR）信号转导的微生物签名的激活是诱导免疫应答的关键。这种反应需要严格的监管。RP 105是TLR同源物，被认为主要是B细胞特异性的，缺乏信号传导结构域。我们在这里报告说，RP 105的表达是广泛的，直接反映了TLR 4的抗原呈递细胞。此外，RP 105是HEK 293细胞中TLR 4信号传导的特异性抑制剂，这是其胞外结构域赋予的功能。值得注意的是，RP 105及其辅助分子MD-1直接与TLR 4信号复合物相互作用，抑制其结合微生物配体的能力。最后，RP 105调节树突状细胞中的TLR 4信号传导以及体内内毒素应答。因此，我们的研究结果确定RP 105作为TLR 4反应的生理负调节剂。
Activation of Toll-like receptor (TLR) signaling by microbial signatures is critical to the induction of immune responses. Such responses demand tight regulation. RP105 is a TLR homolog thought to be mostly B cell specific, lacking a signaling domain. We report here that RP105 expression was wide, directly mirroring that of TLR4 on antigen-presenting cells. Moreover, RP105 was a specific inhibitor of TLR4 signaling in HEK 293 cells, a function conferred by its extracellular domain. Notably, RP105 and its helper molecule, MD-1, interacted directly with the TLR4 signaling complex, inhibiting its ability to bind microbial ligand. Finally, RP105 regulated TLR4 signaling in dendritic cells as well as endotoxin responses in vivo. Thus, our results identify RP105 as a physiological negative regulator of TLR4 responses.