Potent inhibition of dendritic cell differentiation and maturation by vitamin D analogs

We show that the immunosuppressive effects of 1 alpha,25-dihydroxyvitamin D -3 (1 alpha,25(OH)(2)D-3) are due, in part, to inhibition of the T cell sti mulatory functions of dendritic cells (DCs). Addition of 10(-12) and 10(-8) M 1 alpha,25(OH)(2)D-3 to murine DC cultures resulted in a concentration-d ependent 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 1 alpha,25(OH)(2)D-3 reduced DC yield. The capacity of D Cs to induce proliferation of purified allogeneic T cells was reduced by 1 alpha,25(OH)(2)D-3. The vitamin D-3 analog, 1 alpha,25(OH)(2)-16-ene-23-yne -26,27-hexafluoro-19-nor-D-3, exerted identical effects at 100-fold lower c oncentrations. Inhibition of DC maturation and stimulatory function was abs ent in cultures from mice genetically lacking vitamin D receptors (VDR). Vi tamin D analogs effectively reduce DC function via VDR-dependent pathways. (C) 2000 Academic Press.