Regulation of 25-hydroxyvitamin D3-1α-hydroxylase and production of 1α,25-dihydroxyvitamin D3 by human dendritic cells

25-Hydroxyvitamin D-3-1alpha-hydroxylase (25(OH)D-3-1alpha-hydroxylase), the key enzyme of 1alpha,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) production, is expressed in monocyte-derived macrophages (MACs). Here we show for the first time constitutive expression of 25(OH)D-3-1alpha-hydroxylase in monocyte-derived dendritic cells (DCs), which was increased after stimulation with lipopolysaccharide (LPS). Accordingly, DCs showed low constitutive production of 1,25(OH)(2)D-3, but activation by LPS increased 1,25(OH)(2)D-3 synthesis. In addition, 25(OH)D-3-1alpha-hydroxylase expression was found in blood DCs but not in CD34(+)-derived DCs. Next we analyzed the functional consequences of these results. Addition of 1,25(OH)(2)D-3 at concentrations comparable with those produced by DCs inhibited the allostimulatory potential of DCs during the early phase of DC differentiation. However, terminal differentiation decreased the responsiveness of DCs to 1,25(OH)(2)D-3. In conclusion, DCs are able to produce 1,25(OH)(2)D-3 especially following stimulation with LIPS. Terminal maturation renders DCs unresponsive to the effects of 1,25(OH)(2)D-3, but those cells are able to suppress the differentiation of their own precursor cells in a paracrine way through the production of 1,25(OH)(2)D-3. (C) 2003 by The American Society of Hematology.