title: Lgr4/Gpr48 negatively regulates TLR2/4-associated pattern recognition and innate immunity by targeting CD14 expression.
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.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Du
authors.forename: Weijia
authors.initials: W
authors.lastname: Luo
authors.forename: Ruimei
authors.initials: R
authors.lastname: Li
authors.forename: Binghe
authors.initials: B
authors.lastname: Tan
authors.forename: Honghui
authors.initials: H
authors.lastname: Han
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Lu
authors.forename: Dali
authors.initials: D
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Qian
authors.forename: Dekai
authors.initials: D
authors.lastname: Zhang
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D002460:Cell Line; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012772:Shock, Septic / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D015398:Signal Transduction / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: C411562:LGR4 protein, human; C496200:LGR4 protein, mouse; D018950:Lipopolysaccharide Receptors; D043562:Receptors, G-Protein-Coupled; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
keywords: CD14; CREB; G-protein-coupled Receptors (GPCRs); Lgr4; Pathogen-associated Molecular Pattern (PAMP); Sepsis; Toll-like Receptors (TLR)