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Publication : Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105.

First Author  Divanovic S Year  2005
Journal  Nat Immunol Volume  6
Issue  6 Pages  571-8
PubMed ID  15852007 Mgi Jnum  J:98955
Mgi Id  MGI:3580770 Doi  10.1038/ni1198
Citation  Divanovic S, et al. (2005) Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105. Nat Immunol 6(6):571-8
abstractText  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.
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