Tumor Necrosis Factor-α- and IL-4-Independent Development of Langerhans Cell-Like Dendritic Cells from M-CSF-Conditioned Precursors

GM-CSF and transforming growth factor β (TGFβ ) are required for the generation of Langerhans cells (LC), members of the dendritic cell (DC) family. Tumor necrosis factor α (TNFα) 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/TGFβ. The cells express Langerin, CD1a, and CCR6, migrate in response to CCR6 ligand CCL20, and contain Birbeck granules. TNFα and IL-4, added separately or together, have an inhibitory effect on LC differentiation. Cells differentiated in the presence of IL-4 and TNFα 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 TGFβ.