GPR108, an NF-κB activator suppressed by TIRAP, negatively regulates TLR-triggered immune responses.

ABSTRACT: Higher vertebrates have evolved innate and adaptive immune systems to defend against foreign substances and pathogens. Sophisticated regulatory circuits are needed to avoid inappropriate immune responses and inflammation. GPR108 is a seven-transmembrane family protein that activates NF-κB strongly when overexpressed. Surprisingly, its action in a physiological context is that of an antagonist of Toll-like receptor (TLR)-mediated signaling. Cells from Gpr108-null mice exhibit enhanced cytokine secretion and NF-κB and IRF3 signaling, whereas Gpr108-null macrophages reconstituted with GPR108 exhibit blunted signaling. Co-expression of TLRs and GPR108 reduces NF-κB and IFNβ promoter activation compared to expression of either TLRs or GPR108 alone. Upon TLR stimulation GPR108 abundance increase

SUBMITTER: Dong D 

PROVIDER: S-EPMC6192633 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature