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. (C) 2000 Academic Press.