Arrighi, Jean‐François;
Soulas, Caroline;
Hauser, Conrad;
Saeland, Sem;
Chapuis, Bernard;
Zubler, Rudolf H.;
Kindler, Vincent
TNF‐α 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
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Medientyp:
E-Artikel
Titel:
TNF‐α 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
Beteiligte:
Arrighi, Jean‐François;
Soulas, Caroline;
Hauser, Conrad;
Saeland, Sem;
Chapuis, Bernard;
Zubler, Rudolf H.;
Kindler, Vincent
Beschreibung:
<jats:title>Abstract</jats:title><jats:p>CD34<jats:sup>+</jats:sup> 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‐β1, HLA‐DR<jats:sup>+</jats:sup>, CD1a<jats:sup>+</jats:sup>, CD83<jats:sup>–</jats:sup>, CD86<jats:sup>–</jats:sup>, CD80<jats:sup>–</jats:sup> cells. A fraction of them expressed Langerin, Lag, and E‐cadherin, resembling epidermal Langerhans cells (LC). TNF‐α addedfor the last 3 days only marginally induced CD83 expression, but strikingly increased the proportion of immature Langerin<jats:sup>+</jats:sup>CD83<jats:sup>–</jats:sup> LC. Langerin<jats:sup>+</jats:sup>CD83<jats:sup>+</jats:sup> and Langerin<jats:sup>+</jats:sup>CD83<jats:sup>–</jats:sup> cells were functionally distinct, the former internalizing less efficiently Langerin than the latter. Both CD1a<jats:sup>–</jats:sup>CD14<jats:sup>–</jats:sup> and CD1a<jats:sup>–</jats:sup>CD14<jats:sup>+</jats:sup> cells sorted from FLT3‐ligand, thrombopoietin and stem cell factor cultures responded to TNF‐α by an increase of Langerin<jats:sup>+</jats:sup> cells. Thus, TNF‐α rescued LC precursors irrespective of their commitment to the monocytic lineage. When added to GM‐CSF, IL‐4 and TGF β1 containing‐cultures, LPS or IL‐1β also induced significant numbers of Langerin<jats:sup>+</jats:sup>CD83<jats:sup>–</jats:sup> immature cells displaying a low allostimulatory activity, while CD40‐ligand largely promoted highly allostimulatory Langerin<jats:sup>–</jats:sup>CD83<jats:sup>+</jats:sup> cells. Altogether, these data show that in contrast to CD40‐ligand, which induced LC maturation even in presence of TGF‐β1, nonspecific proinflammatory factors such as TNF‐α, IL‐1β or LPS, essentially induced immature LC generation, and little cell activation in the presence of TGF‐β1.</jats:p>