1,25-dihydroxyvitamin D3 selectively modulates tolerogenic properties in myeloid but not plasmacytoid dendritic cells

1,25-Dihydroxyvitamin D-3 (1,25(OH)(2)A(3)) is an immunomodulatory agent inducing dendritic cells (DCs) to become tolerogenic. To further understand its mechanisms of action, we have examined the effects of 1,25(OH)(2)D-3 on tolerogenic properties of blood myeloid (M-Ms) and plasmacytoid (P-Ms) human DC subsets. Exposure of M-DCs to 1,25(OH)(2)D-3 up-regulated production of CCL22, a chemokine attracting regulatory T cells, whereas production of CCL17, the other CCR4 ligand, was reduced. 1,25(OH)2D3 also decreased IL-12p75 production by M-DCs, as expected, and inhibited CCR7 expression. 1,25(OH)2D3 treatment markedly increased CD4(+) suppressor T cell activity while decreasing the capacity of M-DCs to induce Th1 cell development. Surprisingly, 1,25(OH)(2)D-3 did not exert any discernible effect on tolerogenic properties of P-DCs, and even their high production of IFN-alpha was not modulated. In particular, the intrinsically high capacity of P-DCs to induce CD4(+) suppressor T cells was unaffected by 1,25(OH)(2)D-3 Both DC subsets expressed similar levels of the vitamin D receptor, and its ligation by 1,25(OH)(2)D-3 similarly activated the primary response gene cyp24. Interestingly, 1,25(OH)(2)D-3 inhibited NF-kappa B p65 phosphorylation and nuclear translocation in M-DCs but not P-DCs, suggesting a mechanism for the inability of 1,25(OH)(2)D-3 to modulate tolerogenic properties in P-DCs.