The direct action of 1α,25(OH)2-vitamin D3 on purified mouse Langerhans cells

The action of vitamin D3 on Langerhans cells (LCs) is not well understood. Using highly purified murine LCs (>95%), we investigated the direct action of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) on their functions. 1,25(OH)2D3 inhibited the expression of cell surface molecules including I-Ad, CD40, CD80, and CD86, leading to impaired ability of LCs to stimulate allogenic T cells in the mixed leukocyte reaction. Furthermore, this reagent inhibited chemotaxis of LCs to CCL21 and their survival. Interestingly, 1,25(OH)2D3 reduced the IL-10 production by LCs, whereas the production of IL-6 and IL-12p40 upon activation by CD40 ligation was enhanced. With regard to inflammatory cytokines and chemokines, 1,25(OH)2D3 upregulated the production of IL-1β, CCL3, CCL4, and CCL5. The production of Th2-type chemokines, represented by CL17 and CCL22, was inhibited, whereas IFN-γ-triggered production of Th1-type chemokines, represented by CXCL9, CXCL10, and CXCL11, was augmented. These data indicate that the mode of regulation of cytokine and chemokine production in association with 1,25(OH)2D3 treatment seems to be another characteristic discriminating LCs from classical myeloid dendritic cells.