Vitamin D₃ Affects Differentiation, Maturation, and Function of Human Monocyte-Derived Dendritic Cells

Abstract

We studied the effects of 1α,25-dihydroxyvitamin D₃ (1α,25-(OH)₂D₃) on differentiation, maturation, and functions of dendritic cells (DC) differentiated from human monocytes in vitro in the presence of GM-CSF and IL-4 for 7 days. Recovery and morphology were not affected by 1α,25-(OH)₂D₃ up to 100 nM. DC differentiated in the presence of 10 nM 1α,25-(OH)₂D₃ (D₃-DC) showed a marked decrease in the expression of CD1a, while CD14 remained elevated. Mannose receptor and CD32 were significantly increased, and this correlated with an enhancement of endocytic activity. Costimulatory molecules such as CD40 and CD86 were slightly decreased or nonsignificantly affected (CD80 and MHC II). However, after induction of DC maturation with LPS or incubation with CD40 ligand-transfected cells, D₃-DC showed marginal increases in MHC I, MHC II, CD80, CD86, CD40, and CD83. The accessory cell function of D₃-DC in classical MLR was also inhibited. Moreover, allogeneic T cells stimulated with D₃-DC were poor responders in a second MLR to untreated DC from the same or an unrelated donor, thus indicating the onset of a nonspecific hyporesponsivity. In conclusion, our data suggest that 1α,25-(OH)₂D₃ may modulate the immune system, acting at the very first step of the immune response through the inhibition of DC differentiation and maturation into potent APC.