The effects of 1,25-dihydroxyvitamin D3 on markers related to the differentiation and maturation of bone marrow-derived dendritic cells from control and obese mice

Abstract

Vitamin D has been reported to regulate the maturation and function of dendritic cells (DCs). Obesity was shown to be associated with the dysregulation of vitamin D metabolism and malfunction of DCs. We investigated the effects of in vitro 1,25(OH)2D3 treatment (0, 1, or 10 nM) on phenotype and expression of genes related to function of bone marrow-derived DCs (BMDCs) from control and obese mice. C57BL/6 N mice were fed a control or high-fat (10% or 45% kcal fat: CON or HFD) diets for 15 weeks. Differentiation toward DCs was induced with GM-CSF (20 ng/ml) and maturation was induced by LPS (50 ng/ml); 10 nM 1,25(OH)2D3 treatment inhibited BMDC differentiation (CD11c+) and decreased the percentage of mature DCs (MHCIIhighCD11c+ and CD86highCD11c+) in both CON and HFD groups. The Il10 expression in stimulated BMDCs from the CON group increased with the 10 nM 1,25(OH)2D3 treatment, but not in those from the HFD group. The Il12b mRNA levels in stimulated BMDCs were lower in the HFD group than in the CON group. In conclusion, lower levels of Cd 40, Cd83 and Il12 mRNA in LPS-stimulated BMDCs from obese mice suggest malfunction of DCs as antigen presenting cells. 1,25(OH)2D3 treatment inhibited the differentiation and maturation of BMDCs in both control and obese mice. Differential effects of 1,25(OH)2D3 on the expression of Il10 between control and obese mice suggest that regulation of immune response by vitamin D could be influenced by obesity.