Cho Da Hye, Lee Ga Young, An Jeong Hee, Han Sung Nim
Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, South Korea.
Research Institute of Human Ecology, Seoul National University, Seoul, South Korea.
IUBMB Life. 2022 May;74(5):378-390. doi: 10.1002/iub.2592. Epub 2022 Jan 10.
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 (1,25(OH) D ), 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) D 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) D . With 1,25(OH) D 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) D 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) D on glycolysis.
维生素D影响树突状细胞（DCs）的分化、成熟和激活。肥胖相关的免疫功能障碍与免疫细胞的代谢变化有关。本研究的目的是探讨维生素D和肥胖对骨髓来源的树突状细胞（BMDCs）免疫反应及免疫代谢相关标志物的影响。从瘦小鼠和肥胖小鼠中分离骨髓细胞（BMCs），并用重组小鼠粒细胞-巨噬细胞集落刺激因子（rmGM-CSF）培养BMCs以生成BMDCs。用1或10 nM的1,25-二羟基维生素D（1,25(OH)₂D₃）处理BMDCs，并用脂多糖（LPS，50 ng/ml）刺激24小时以诱导其成熟。测定细胞表型、细胞因子产生以及参与Akt/mTOR信号通路和糖酵解途径的蛋白质和基因的表达。1,25(OH)₂D₃处理抑制了瘦小鼠和肥胖小鼠中BMDCs的分化（CD11c%）、与DC功能相关的表型（MHC II类和CD86）的表达以及IL-12p70的产生。1,25(OH)₂D₃增加了程序性死亡受体配体1（PD-L1）的表达以及IL-10/IL-12p70的比值。经1,25(OH)₂D₃处理后，Akt/mTOR信号通路受到抑制，与糖酵解相关的基因（葡萄糖转运蛋白1（Glut1）、6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶4（Pfkfb⁴）和缺氧诱导因子1α（Hif1A））的表达增加。1,25(OH)₂D₃处理后观察到的糖酵解相关基因的上调似乎与诱导瘦小鼠和肥胖小鼠BMDCs的耐受性特征有关，并且Hif1A似乎在传递1,25(OH)₂D₃对糖酵解的作用方面具有潜在作用。
