title: Tumor necrosis factor-alpha- and IL-4-independent development of Langerhans cell-like dendritic cells from M-CSF-conditioned precursors.
abstract: GM-CSF and transforming growth factor beta (TGFbeta ) are required for the generation of Langerhans cells (LC), members of the dendritic cell (DC) family. Tumor necrosis factor alpha (TNFalpha) and IL-4 can enhance LC differentiation from human monocytes or CD34(+) progenitors. Here, we show that M-CSF-cultured DC precursors derived from CD34(+) progenitors resemble dermal CD14(+) cells and readily convert to LC-like DC in GM-CSF/TGFbeta. The cells express Langerin, CD1a, and CCR6, migrate in response to CCR6 ligand CCL20, and contain Birbeck granules. TNFalpha and IL-4, added separately or together, have an inhibitory effect on LC differentiation. Cells differentiated in the presence of IL-4 and TNFalpha express low levels of CCR7. This suggests that M-CSF-conditioned DC precursors retain the capacity to efficiently undergo a differentiation program, giving rise to LC-like DC solely through the effect of GM-CSF and TGFbeta.
authors.affiliation: INSERM U255, IFR58, Centre de Recherches Biomédicales des Cordeliers, Université Pierre et Marie Curie (Paris 6) et René Descartes (Paris 5), Paris, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Barbaroux
authors.forename: Wing-Hong
authors.initials: WH
authors.lastname: Kwan
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Allam
authors.forename: Natalija
authors.initials: N
authors.lastname: Novak
authors.forename: Thomas
authors.initials: T
authors.lastname: Bieber
authors.forename: Wolf H
authors.initials: WH
authors.lastname: Fridman
authors.forename: Richard
authors.initials: R
authors.lastname: Groves
authors.forename: Chris G
authors.initials: CG
authors.lastname: Mueller
mesh_terms: D015703:Antigens, CD; D018949:Antigens, CD1 / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis; D002454:Cell Differentiation; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D020405:Dermis / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D007801:Langerhans Cells / Q000166:cytology*; D037181:Lectins, C-Type / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D037241:Mannose-Binding Lectins / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D018949:Antigens, CD1; D018952:Antigens, CD34; D000954:Antigens, Surface; C108355:CCL20 protein, human; C106311:CCR6 protein, human; C419393:CD1a antigen; C121916:CD207 protein, human; D002352:Carrier Proteins; D054418:Chemokine CCL20; D019742:Chemokines, CC; D016207:Cytokines; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D019402:Macrophage Inflammatory Proteins; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor