Micro-environmental signals directing human epidermal Langerhans cell differentiation

Decisive factors for LC development are provided by the epidermal niche. Keratinocytes (KC) in the epidermal microenvironment provide key factors involved in the differentiation and maintenance of CD1a+CD207+ LCs, including the TGF-β family members BMP7 and TGF-β1, Notch ligands and E-cadherin. BMP7 expression is maintained in adult basal keratinocyte layers, whereas TGF-β1 is mainly provided by supra-basal keratinocyte layers. These extrinsic KC-derived factors induce the differentiation of non-activated LCs via transcription factors RUNX3 and PU.1; moreover VDR, E-cadherin/β-catenin, AXL and miRNAs seem to functionally participate in LC differentiation and maintenance.