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首页> 外文期刊>Nature immunology >Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105
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Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105

机译:Toll样受体同源物RP105对Toll样受体4信号的负调控

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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.
机译:微生物签名激活Toll样受体(TLR)信号对于诱导免疫反应至关重要。这种反应需要严格的监管。 RP105是一种TLR同源物,被认为主要是B细胞特异性的,缺乏信号传导域。我们在这里报告说,RP105表达很宽,直接反映了抗原呈递细胞上TLR4的表达。此外,RP105是HEK 293细胞中TLR4信号转导的特异性抑制剂,该功能由其细胞外结构域赋予。值得注意的是,RP105及其辅助分子MD-1直接与TLR4信号复合物相互作用,从而抑制了其与微生物配体结合的能力。最后,RP105调节树突状细胞中的TLR4信号传导以及体内内毒素反应。因此,我们的结果确定RP105为TLR4反应的生理阴性调节剂。

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