title: TNF-alpha induces the generation of Langerin/(CD207)+ immature Langerhans-type dendritic cells from both CD14-CD1a and CD14+CD1a- precursors derived from CD34+ cord blood cells.
abstract: CD34+ cell-derived hematopoietic precursors amplified with FLT3-ligand, thrombopoietin and stem cell factor became, after a 6-day induction with GM-CSF, IL-4 and TGF-beta1, HLA-DR+, CD1a+, CD83-, CD86-, CD80- cells. A fraction of them expressed Langerin, Lag, and E-cadherin, resembling epidermal Langerhans cells (LC). TNF-alpha added for the last 3 days only marginally induced CD83 expression, but strikingly increased the proportion of immature Langerin+CD83- LC. Langerin+CD83+ and Langerin+CD83- cells were functionally distinct, the former internalizing less efficiently Langerin than the latter. Both CD1a-CD14- and CD1a-CD14+ cells sorted from FLT3-ligand, thrombopoietin and stem cell factor cultures responded to TNF-alpha by an increase of Langerin+ cells. Thus, TNF-alpha rescued LC precursors irrespective of their commitment to the monocytic lineage. When added to GM-CSF, IL-4 and TGF-beta1 containing-cultures, LPS or IL-1beta also induced significant numbers of Langerin+CD83- immature cells displaying a low allostimulatory activity, while CD40-ligand largely promoted highly allostimulatory Langerin-CD83+ cells. Altogether, these data show that in contrast to CD40-ligand, which induced LC maturation even in presence of TGF-beta1, nonspecific proinflammatory factors such as TNF-alpha, IL-1 or LPS, essentially induced immature LC generation, and little cell activation in the presence of TGF-beta1.
authors.affiliation: Department of Dermatolology, Geneva University Hospital, 25 Micheli-du-Crest, CH-12ll Geneva 14, Switzerland.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Arrighi
authors.forename: Caroline
authors.initials: C
authors.lastname: Soulas
authors.forename: Conrad
authors.initials: C
authors.lastname: Hauser
authors.forename: Sem
authors.initials: S
authors.lastname: Saeland
authors.forename: Bernard
authors.initials: B
authors.lastname: Chapuis
authors.forename: Rudolf H
authors.initials: RH
authors.lastname: Zubler
authors.forename: Vincent
authors.initials: V
authors.lastname: Kindler
mesh_terms: D015703:Antigens, CD; D018949:Antigens, CD1 / Q000276:immunology*; D018952:Antigens, CD34 / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D005312:Fetal Blood / Q000276:immunology; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D037241:Mannose-Binding Lectins; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D018949:Antigens, CD1; D018952:Antigens, CD34; D000954:Antigens, Surface; C419393:CD1a antigen; C121916:CD207 protein, human; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D037241:Mannose-Binding Lectins; D014409:Tumor Necrosis Factor-alpha