title: Sequential involvement of CCR2 and CCR6 ligands for immature dendritic cell recruitment: possible role at inflamed epithelial surfaces.
abstract: To reach the site of antigen deposition at epithelial surfaces, dendritic cells (DC) have to traverse the endothelial barrier, progress through the tissue (i.e., dermis) and cross the dermo-epithelial junction (basal membrane). In the present study, we demonstrate that (1) circulating blood DC and monocytes express high levels of CCR2 and primarily respond to monocyte chemotactic protein (MCP) and not to macrophage inflammatory protein (MIP)-3alpha/CCL20; (2) while the CD34(+) hematopoietic progenitor cells (HPC)-derived CD1a(+) precursors committed to Langerhans cell differentiation primarily respond to MIP-3alpha/CCL20, the HPC-derived CD14(+) precursors respond to both MCP and MIP-3alpha/CCL20; (3) in concordance with the sequential expression of CCR2 and CCR6, the HPC-derived CD14(+) precursors initially acquire the ability to migrate in response to MCP-4/CCL13 and subsequently in response to MIP-3alpha/CCL20; and (4) in vivo, in inflamed epithelium, MCP-4/CCL13 and MIP-3alpha/CCL20 form complementary gradients, with MCP-4/CCL13 expressed in basal epithelial cells at the contact of blood vessels, while MIP-3alpha/CCL20 expression is restricted to epithelial cells bordering the external milieu. These observations suggest that the recruitment of DC to the site of infection is controlled by the sequential action of different chemokines: (i) CCR2(+) circulating DC or DC precursors are mobilized into the tissue via the expression of MCP by cells lining blood vessels, and (ii) these cells traffic from the tissue to the site of pathogen invasion via the production of MIP-3alpha/CL20 by epithelial cells and the up-regulation of CCR6 in response to the tissue environment.
authors.affiliation: Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Vanbervliet
authors.forename: Bernhard
authors.initials: B
authors.lastname: Homey
authors.forename: Isabelle
authors.initials: I
authors.lastname: Durand
authors.forename: Catherine
authors.initials: C
authors.lastname: Massacrier
authors.forename: Smina
authors.initials: S
authors.lastname: Aït-Yahia
authors.forename: Odette
authors.initials: O
authors.lastname: de Bouteiller
authors.forename: Alain
authors.initials: A
authors.lastname: Vicari
authors.forename: Christophe
authors.initials: C
authors.lastname: Caux
mesh_terms: D018952:Antigens, CD34; D015415:Biomarkers; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology / Q000494:pharmacology; D002633:Chemotaxis; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D018945:Monocyte Chemoattractant Proteins / Q000276:immunology* / Q000494:pharmacology; D054390:Receptors, CCR2; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000276:immunology* / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; C099677:CCL13 protein, human; C515334:CCR2 protein, human; C106311:CCR6 protein, human; D018925:Chemokines; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D018945:Monocyte Chemoattractant Proteins; D054390:Receptors, CCR2; D054399:Receptors, CCR6; D019707:Receptors, Chemokine