title: Characterization of CCL20 secretion by human epithelial vaginal cells: involvement in Langerhans cell precursor attraction.
abstract: Mucosa represents the main site of pathogen/cell interactions. The two main types of cells forming the epithelial structure [epithelial cells and Langerhans cells (LC)] coordinate the first defense responses to avoid infection. To evaluate the involvement of epithelial cells in the early steps leading to a specific adaptive immune response, we have studied the interactions between vaginal epithelial and LC through the establishment of a human vaginal epithelial mucosa. We demonstrate that normal human vaginal epithelial cells constitutively secrete the chemokine macrophage inflammatory protein 3alpha/CC chemokine ligand 20 (CCL20), known to recruit LC precursors (LCps) selectively via its cognate CC chemokine receptor 6 (CCR6). This secretion is up-regulated by the proinflammatory cytokine interleukin-1beta through the nuclear factor-kappaB pathway. Similar results were obtained with the human vaginal epithelial cell line SiHa, which displays numerous homologies with normal vaginal cells. The chemotactic activity of the secreted CCL20 was demonstrated by its ability to attract LCp CCR6+. Moreover, the use of neutralizing polyclonal antibodies directed against the CCL20 molecule abolished this migration completely, suggesting that CCL20 is the main attracting factor for LCps, which is produced by the vaginal cells. These data indicate that vaginal epithelial cells play an important role in the immunological defense by attracting immune cells to the site of epithelial/pathogen contact.
authors.affiliation: Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Faculté de Médecine J. Lisfranc, St Etienne, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Cremel
authors.forename: Willy
authors.initials: W
authors.lastname: Berlier
authors.forename: Hind
authors.initials: H
authors.lastname: Hamzeh
authors.forename: Fabrice
authors.initials: F
authors.lastname: Cognasse
authors.forename: Philip
authors.initials: P
authors.lastname: Lawrence
authors.forename: Christian
authors.initials: C
authors.lastname: Genin
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Bernengo
authors.forename: Claude
authors.initials: C
authors.lastname: Lambert
authors.forename: Marie-Caroline
authors.initials: MC
authors.lastname: Dieu-Nosjean
authors.forename: Olivier
authors.initials: O
authors.lastname: Delézay
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002633:Chemotaxis / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007375:Interleukin-1 / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000276:immunology; D013234:Stem Cells / Q000276:immunology*; D014621:Vagina / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D000906:Antibodies; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D054399:Receptors, CCR6; D019707:Receptors, Chemokine