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

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-β1, HLADR+, CD1a+, CD83-, CD86-, CD80- cells. A fraction of them expressed Langerin, Lag, and E-cadherin, resembling epidermal Langerhans cells (LC). TNF-α 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-α by an increase of Langerin+ cells. Thus, TNF-α rescued LC precursors irrespective of their commitment to the monocytic lineage. When added to GM-CSF, IL-4 and TGFβ1 containing-cultures, LPS or IL-1β 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-β1, non-specific 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.