Over the past thirty years,the importance of chemokines and their seven-transmembrane G protein-coupled receptors(GPCRs)has been increasingly recognized.Chemokine interactions with receptors trigger signaling pathway ...Over the past thirty years,the importance of chemokines and their seven-transmembrane G protein-coupled receptors(GPCRs)has been increasingly recognized.Chemokine interactions with receptors trigger signaling pathway activity to form a network fundamental to diverse immune processes,including host homeostasis and responses to disease.Genetic and nongenetic regulation of both the expression and structure of chemokines and receptors conveys chemokine functional heterogeneity.Imbalances and defects in the system contribute to the pathogenesis of a variety of diseases,including cancer,immune and inflammatory diseases,and metabolic and neurological disorders,which render the system a focus of studies aiming to discover therapies and important biomarkers.The integrated view of chemokine biology underpinning divergence and plasticity has provided insights into immune dysfunction in disease states,including,among others,coronavirus disease 2019(COVID-19).In this review,by reporting the latest advances in chemokine biology and results fromanalyses of a plethora of sequencing-based datasets,we outline recent advances in the understanding of the genetic variations and nongenetic heterogeneity of chemokines and receptors and provide an updated view of their contribution to the pathophysiological network,focusing on chemokine-mediated inflammation and cancer.Clarification of the molecular basis of dynamic chemokine-receptor interactions will help advance the understanding of chemokine biology to achieve precision medicine application in the clinic.展开更多
基金the National Natural Science Foundation of China(NSFC Grant No.81872021,32200462)Beijing Jiaotong University undergraduate innovation and entrepreneurship training project(No.220171097,220171072,220171037,220171088,220171104)+3 种基金R&D Program of Beijing Municipal Education Commission(Grant No.KM202110025004)Beijing Hospitals Authority Youth Programme(grant No.QML20231602)JH,KC and JMW were also funded in part by Federal funds from the National Cancer Institute,National Institutes of Health(under Contract No.HHSN261200800001E)the Intramural Research Programs of the NCI,CCR,and NIH.
文摘Over the past thirty years,the importance of chemokines and their seven-transmembrane G protein-coupled receptors(GPCRs)has been increasingly recognized.Chemokine interactions with receptors trigger signaling pathway activity to form a network fundamental to diverse immune processes,including host homeostasis and responses to disease.Genetic and nongenetic regulation of both the expression and structure of chemokines and receptors conveys chemokine functional heterogeneity.Imbalances and defects in the system contribute to the pathogenesis of a variety of diseases,including cancer,immune and inflammatory diseases,and metabolic and neurological disorders,which render the system a focus of studies aiming to discover therapies and important biomarkers.The integrated view of chemokine biology underpinning divergence and plasticity has provided insights into immune dysfunction in disease states,including,among others,coronavirus disease 2019(COVID-19).In this review,by reporting the latest advances in chemokine biology and results fromanalyses of a plethora of sequencing-based datasets,we outline recent advances in the understanding of the genetic variations and nongenetic heterogeneity of chemokines and receptors and provide an updated view of their contribution to the pathophysiological network,focusing on chemokine-mediated inflammation and cancer.Clarification of the molecular basis of dynamic chemokine-receptor interactions will help advance the understanding of chemokine biology to achieve precision medicine application in the clinic.
