Lgr4/Gpr48 negatively regulates TLR2/4-associated pattern recognition and innate immunity by targeting CD14 expression. Academic Article uri icon

abstract

  • The recognition of pathogen-associated molecular patterns by Toll-like receptors (TLRs) is pivotal in both innate and adaptive immune responses. Here we demonstrate that deletion of Lgr4/Gpr48 (G-protein-coupled receptor 48), a seven-transmembrane glycoprotein hormone receptor, potentiates TLR2/4-associated cytokine production and attenuates mouse resistance to septic shock. The expression of CD14, a co-receptor for TLR2/4-associated pathogen-associated molecular patterns, is increased significantly in Lgr4-deficient macrophages, which is consistent with the increased immune response, whereas the binding activity of cAMP-response element-binding protein is decreased significantly in Lgr4-deficient macrophages, which up-regulate the expression of CD14 at the transcriptional level. Together, our data demonstrate that Lgr4/Gpr48 plays a critical role in modulating the TLR2/4 signaling pathway and represents a useful therapeutic approach of targeting Lgr4/Gpr48 in TLR2/4-associated septic shock and autoimmune diseases.

published proceedings

  • J Biol Chem

altmetric score

  • 3

author list (cited authors)

  • Du, B., Luo, W., Li, R., Tan, B., Han, H., Lu, X., ... Liu, M

citation count

  • 33

complete list of authors

  • Du, Bing||Luo, Weijia||Li, Ruimei||Tan, Binghe||Han, Honghui||Lu, Xiaoling||Li, Dali||Qian, Min||Zhang, Dekai||Zhao, Yongxiang||Liu, Mingyao

publication date

  • May 2013