Langerhans cells: Straight from blood to skin?

Abstract

In this issue of Blood, Milne et al1 report a developmental pathway for human Langerhans cells from circulating CD14-CD1c+ dendritic cell (DC) precursors in peripheral blood. The Langerhans cell progeny, expressing CD207 (langerin) and bearing the hallmark Birbeck granules, result from culture in granulocyte macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-β1 (TGF-β1) and/or bone morphogenetic protein 7 (BMP7). A similar study by Martínez-Cingolani et al,2 also published recently in Blood, identified the same circulating CD14-CD1c+ Langerhans cell precursors. These authors used a different anti-CD1c monoclonal antibody (BDCA-1). In that study, TGF-β1 synergized with thymic stromal lymphopoietin (TSLP) to yield similar Langerhans cell progeny. Both groups used fetal calf serum (FCS), however, which affects differentiation and maturation by unknown mechanisms and is not physiologically comparable to human plasma in vivo. Controls with FCS-containing medium, but without cytokines, indicated that FCS was not the driver of the conversion. However, Milne et al1 could not generate Langerhans cell progeny by culture in X-Vivo medium without FCS, despite inclusion of GM-CSF, TGF-β1, and BMP7, all of which, together with TSLP, are epithelial cell-derived cytokines under physiologic conditions.