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.