title: Human immature monocyte-derived dendritic cells express the G protein-coupled receptor GPR105 (KIAA0001, P2Y14) and increase intracellular calcium in response to its agonist, uridine diphosphoglucose.
abstract: Dendritic cells (DC) are essential to the initiation of an immune response due to their unique ability to take-up and process Ag, translocate to lymph nodes, and present processed Ag to naive T cells. Many chemokines, chemokine receptors and other G protein-coupled receptors (GPCRs) are implicated in these various aspects of DC biology. Through microarray analysis, we compared expression levels of chemokines, their cognate receptors, and selected GPCRs in human monocytes and in vitro monocyte-derived immature and mature DC. Hierarchical clustering of gene expression clearly distinguishes the three cell types, most notably highlighting exceptional levels of expression of the GPCR GPR105 within the immature monocyte-derived DC (MDDC) gene cluster. Little or no expression was observed within the monocyte and mature MDDC cluster. Putative functionality of the GPR105 receptor was demonstrated by an observed calcium flux in immature MDDC treated with the potent GPR105 agonist, uridine 5'-diphosphoglucose (UDP-glucose), while no response to the nucleotide sugar was seen in monocytes and mature MDDC. This UDP-glucose-induced calcium response was, at least in part, pertussis toxin-sensitive. Moreover, immature MDDC from some donors treated with UDP-glucose exhibit an increase in expression of the costimulatory molecule CD86, which correlates with the intensity of the UDP-glucose-induced calcium flux. Together, these data demonstrate differential expression of GPR105 on immature and mature MDDC and suggest a role for the receptor and its agonist ligand in DC activation.
authors.affiliation: Celltech R&D, Slough, Berkshire, United Kingdom.
authors.forename: Lisa
authors.initials: L
authors.lastname: Skelton
authors.forename: Mike
authors.initials: M
authors.lastname: Cooper
authors.forename: Marianne
authors.initials: M
authors.lastname: Murphy
authors.forename: Adam
authors.initials: A
authors.lastname: Platt
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D051940:B7-2 Antigen; D001693:Biological Transport, Active; D015415:Biomarkers / Q000032:analysis; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D003911:Dextrans / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D005810:Multigene Family / Q000276:immunology; D037342:Pertussis Toxin / Q000494:pharmacology; D058910:Purinergic P2 Receptor Agonists; D043562:Receptors, G-Protein-Coupled; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis* / Q000502:physiology; D058470:Receptors, Purinergic P2Y; D015854:Up-Regulation; D014532:Uridine Diphosphate Glucose / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; D015415:Biomarkers; D002118:Calcium; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate; D019204:GTP-Binding Proteins; D008562:Membrane Glycoproteins; D037342:Pertussis Toxin; D058910:Purinergic P2 Receptor Agonists; D043562:Receptors, G-Protein-Coupled; D018048:Receptors, Purinergic P2; D058470:Receptors, Purinergic P2Y; D014532:Uridine Diphosphate Glucose; C497964:CD86 protein, human; C015219:fluorescein isothiocyanate dextran; C518528:P2Y14 receptor, human