1,25-Dihydroxyvitamin D3 alters the profile of bone marrow-derived dendritic cells of NOD mice

Abstract

1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] prevents autoimmune diabetes in nonobese diabetic (NOD) mice. A major target for 1,25(OH)(2)D(3) in the immune system is the dendritic cell (DC). Since important DC abnormalities have been described in NOD mice, we investigated the effects of 1,25(OH)(2)D(3) on the yield and phenotype of DCs generated from bone marrow of NOD mice compared to control congenic nonobese diabetes-resistant (NOR) mice. In both mouse strains, exposure of the bone marrow-derived cells to 1,25(OH)(2)D(3) increased the proportion of CD11c(+) DCs after culture. Surface expression of MHC II, CD86, and CD54 on NOR-derived DCs was decreased after 1,25(OH)(2)D(3) treatment, while CD40 remained unchanged. On NOD-derived DCs, 1,25(OH)(2)D(3) only inhibited the expression of MHC II and CD86. 1,25(OH)(2)D(3) inhibited IL-12 and IL-10 secretion after IFNgamma and LPS stimulation. In vitro treatment with 1,25(OH)(2)D(3) alters DC yield from bone marrow cultures and alters the phenotype of the cells in NOD as well as in NOR mice. NOD-derived DCs were more resistant to the 1,25(OH)(2)D(3) effects than were NOR-derived DCs.