The direct action of 1α,25(OH) 2-vitamin D 3 on purified mouse Langerhans cells

Abstract

The action of vitamin D 3 on Langerhans cells (LCs) is not well understood. Using highly purified murine LCs (>95%), we investigated the direct action of 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2D 3) on their functions. 1,25(OH) 2D 3 inhibited the expression of cell surface molecules including I-A d, 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) 2D 3 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) 2D 3 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) 2D 3 treatment seems to be another characteristic discriminating LCs from classical myeloid dendritic cells.