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Published online before print April 14, 2005

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0305147

Received for publication March 15, 2005.

Accepted for publication March 20, 2005.

Article

Characterization of CCL20 secretion by human epithelial vaginal cells: involvement in Langerhans cell precursor attraction

Magali Cremel ^*, Willy Berlier ^*, Hind Hamzeh ^*, Fabrice Cognasse ^*, Philip Lawrence ^*, Christian Genin ^*, Jean-Claude Bernengo , Claude Lambert , Marie-Caroline Dieu-Nosjean , and Olivier Delézay ^*@

*Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Faculté de Médecine J. Lisfranc, St Etienne, France; Centre Commun de Quantimétrie, Université Claude Bernard Lyon 1, France; Laboratoire d’Immunologie Clinique, CHU, St Etienne, France; and INSERM U255, Centre de Recherches Biomédicales des Cordeliers, Paris, France

^@ To whom correspondence should be addressed. E-mail: delezay{at}univ-st-etienne.fr.

	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 adaptative 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 3/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-1 through the nuclear factor-B 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.

Key Words: chemokine • vaginal epithelial cells • mucosal model

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