The effects of 1,25(<scp>OH</scp>)<scp><sub>2</sub>D<sub>3</sub></scp> treatment on immune responses and intracellular metabolic pathways of bone <scp>marrow‐derived</scp> dendritic cells from lean and obese mice
Da Hye Cho, Ga Young Lee, Jeong Hee An, Sung Nim Han
Abstract
Abstract Vitamin D affects differentiation, maturation, and activation of dendritic cells (DCs). Obesity‐related immune dysfunction is associated with metabolic changes in immune cells. Objectives of the study are to investigate the effects of vitamin D and obesity on immune responses and markers related to immunometabolism of bone marrow‐derived dendritic cells (BMDCs). Bone marrow cells (BMCs) were isolated from lean and obese mice, and BMDCs were generated by culturing BMCs with rmGM‐CSF. BMDCs were treated with 1 or 10 nM of 1,25‐dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), and maturation was induced by LPS (50 ng/ml) stimulation for 24 hr. Cell phenotypes, cytokine productions, and expression of proteins and genes involved in Akt/mTOR signaling pathway and glycolytic pathway were determined. 1,25(OH) 2 D 3 treatment inhibited differentiation of BMDCs (CD11c + %), expression of phenotypes related with DC function (MHC class II and CD86) and production of IL‐12p70 in both lean and obese mice. The expression of PD‐L1 and the ratio of IL‐10/IL‐12p70 were increased by 1,25(OH) 2 D 3 . With 1,25(OH) 2 D 3 treatment, Akt/mTOR signaling pathway was suppressed, and expression of genes related to glycolysis ( Glut1 , Pfkfb4 , and Hif1A ) was increased. The upregulation of glycolysis‐related genes observed with 1,25(OH) 2 D 3 treatment seems to be associated with the induction of tolerogenic features of BMDCs from lean and obese mice, and Hif1A seems to have a potential role in conveying the effect of 1,25(OH) 2 D 3 on glycolysis.