Lgr4/Gpr48 Negatively Regulates TLR2/4-associated Pattern Recognition and Innate Immunity by Targeting CD14 Expression
Lgr4/Gpr48 Negatively Regulates TLR2/4-associated Pattern Recognition and Innate Immunity by Targeting CD14 Expression
复制标题
Lgr4/Gpr48 通过靶向 CD14 表达负调节 TLR2/4 相关模式识别和先天免疫
DOI：
10.1074/jbc.m113.455535
复制
发表时间：
2013-05-24
影响因子：
4.8
通讯作者：
Liu, Mingyao
中科院分区：
文献类型：
--
作者：
Du, Bing;Luo, Weijia;Liu, Mingyao
Toll样受体（TLRs）对病原体相关分子模式的识别在先天性和适应性免疫应答中都至关重要。在此我们证明，七次跨膜糖蛋白激素受体Lgr4/Gpr48（G蛋白偶联受体48）的缺失增强了与TLR2/4相关的细胞因子产生，并减弱了小鼠对脓毒症休克的抵抗力。TLR2/4相关病原体相关分子模式的共受体CD14的表达在Lgr4缺陷型巨噬细胞中显著增加，这与免疫应答增强一致，而在Lgr4缺陷型巨噬细胞中，环磷腺苷效应元件结合蛋白的结合活性显著降低，它在转录水平上调CD14的表达。总之，我们的数据表明Lgr4/Gpr48在调节TLR2/4信号通路中起关键作用，并代表了一种在TLR2/4相关脓毒症休克和自身免疫性疾病中靶向Lgr4/Gpr48的有用治疗方法。
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.