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Title

Airway epithelial IL-15 transforms monocytes into dendritic cells

Authors
Obregon, Carolina
van Leer, Coretta
Geiser, Thomas
Published in American Journal of Respiratory Cell and Molecular Biology. 2007, vol. 37, no. 1, p. 75-84
Abstract IL-15 has recently been shown to induce the differentiation of functional dendritic cells (DCs) from human peripheral blood monocytes. Since DCs lay in close proximity to epithelial cells in the airway mucosa, we investigated whether airway epithelial cells release IL-15 in response to inflammatory stimuli and thereby induce differentiation and maturation of DCs. Alveolar (A549) and bronchial (BEAS-2B) epithelial cells produced IL-15 spontaneously and in a time- and dose-dependent manner after stimulation with IL-1beta, IFN-gamma, or TNF-alpha. Airway epithelial cell supernatants induced an increase of IL-15Ralpha gene expression in ex vivo monocytes, and stimulated DCs enhanced their IL-15Ralpha gene expression up to 300-fold. Airway epithelial cell-conditioned media induced the differentiation of ex vivo monocytes into partially mature DCs (HLA-DR+, DC-SIGN+, CD14+, CD80-, CD83+, CD86+, CCR3+, CCR6(+), CCR7-). Based on their phenotypic (CD123+, BDCA2+, BDCA4+, BDCA1(-), CD1a-) and functional properties (limited maturation upon stimulation with LPS and limited capacity to induce T cell proliferation), these DCs resembled plasmacytoid DCs. The effects of airway epithelial cell supernatants were largely blocked by a neutralizing monoclonal antibody to IL-15. Thus, our results demonstrate that airway epithelial cell-conditioned media have the capacity to differentiate monocytes into functional DCs, a process substantially mediated by epithelial-derived IL-15.
Keywords Antibodies, Monoclonal/chemistryBronchi/metabolismCell DifferentiationCulture Media, ConditionedDendritic Cells/cytology/drug effectsEpithelium/metabolismHumansInflammationInterferon-gamma/metabolismInterleukin-15/administration & dosage/metabolismInterleukin-15 Receptor alpha Subunit/metabolismLipopolysaccharides/metabolismMonocytes/cytology/drug effectsPulmonary Alveoli/metabolismTumor Necrosis Factor-alpha/metabolism
Identifiers
PMID: 17363780
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Research group Mucoviscidose et jonctions GAP (229)
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REGAMEY, Nicolas et al. Airway epithelial IL-15 transforms monocytes into dendritic cells. In: American Journal of Respiratory Cell and Molecular Biology, 2007, vol. 37, n° 1, p. 75-84. https://archive-ouverte.unige.ch/unige:27052

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Deposited on : 2013-03-26

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