Induction of langerin+ Langerhans cell-like cells expressing reduced TLR3 from CD34+ cord blood cells stimulated with GM-CSF,TGF-β1,and TNF-α

Abstract

Langerhans cells (LCs),a subset of dendritic cells (DCs),reside in body surface presenting antigens from various pathogens and activate immune system after migrating to vicinal lymph nodes. We recently demonstrated that the E-cadherin interaction allowed peripheral blood (PB) CD14+ cells to differentiate into LC-like cells that closely resemble primary LCs. Here,with a combination of GM-CSF,TGF-β,and TNF-α,we induced LC-like cells from umbilical cord blood (UCB)- derived CD34+ cells and compared them with those induced from PB CD14+ cells. In contrast to PB CD14+ cell-derived LC-like cells with an undetectable surface level of toll-like receptor (TLR)4 and an unresponsiveness feature to bacterial lipopolysaccharide (LPS),CB CD34+ cellsderived LC like cells expressed a low,but apparent,surface level of TLR4 and a reduced level of intracellular TLR3. Consistent with this result,they responded to bacterial LPS,but poorly to poly(I:C) reflecting viral RNA. These findings suggest that LC-precursors from circulating PB CD14+ cells seem to be arranged in the outer barrier of skin,while LC-precursors from local undifferentiated UCB-derived CD34+ cells may be arranged in the inner barrier of mucosal tissues and work together to combat against external pathogens as well as internal malignancies throughout body surface.