Potent Inhibition of Dendritic Cell Differentiation and Maturation by Vitamin D Analogs

We show that the immunosuppressive effects of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) are due, in part, to inhibition of the T cell stimulatory functions of dendritic cells (DCs). Addition of 10−12 and 10−8 M 1α,25(OH)2D3 to murine DC cultures resulted in a concentration-dependent reduction in levels of class II MHC and the co-stimulatory ligands B7-1, B7-2, and CD40 without affecting the number of DCs generated. Higher concentrations of 1α,25(OH)2D3 reduced DC yield. The capacity of DCs to induce proliferation of purified allogeneic T cells was reduced by 1α,25(OH)2D3. The vitamin D3 analog, 1α,25(OH)2-16-ene-23-yne-26,27-hexafluoro-19-nor-D3, exerted identical effects at 100-fold lower concentrations. Inhibition of DC maturation and stimulatory function was absent in cultures from mice genetically lacking vitamin D receptors (VDR). Vitamin D analogs effectively reduce DC function via VDR-dependent pathways.