A profile of pro-inflammatory cytokine expression in human Delta-1-induced monocyte-derived Langerhans cell-like dendritic cells after stimulation with Toll-like receptor ligands

Abstract

Monocyte-derived Langerhans cell-like dendritic cells (Mo-LCs) are involved in epidermal disorders such as psoriasis in murine models. However, the roles of Mo-LCs in the pathogenesis of psoriasis in humans remain unclear. Also, the contribution of notch ligand delta-like 1 (DLL-1), expressed on keratinocytes, to Mo-LC functions requires clarification. Here, we established a new method of stimulating Mo-LCs derived from CD14+ monocytes with immobilized human DLL-1 to generate induced Mo-LCs (DI (+)Mo-LCs). The DI (+) Mo-LCs were compared to the dendritic cells derived from monocytes (Mo-DCs) cultured with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF), and M1 macrophages (Mφ) derived from monocytes cultured with GM-CSF. The DI (+)Mo-LCs were found to produce significant amounts of IL15, IL23A, and interferon-β (IFNB1) in response to the Toll-like receptor (TLR)3 agonist Polyinosinic-polycytidylic acid (Poly (I:C)) or TLR4 agonist lipopolysaccharide (LPS) despite their low expression of tumor necrosis factor (TNF). In conclusion, we have established a new method to generate DI (+)Mo-LCs. We have also discovered that DI (+)Mo-LCs have a unique capacity for producing IL15 and IL23A, which are related to the pathogenesis of psoriasis. Our data contribute to a better understanding of the roles of Mo-LCs in epidermal defense and pathogenesis.