Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Republic of Korea.
Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Republic of Korea; Research Institute of Human Ecology, College of Human Ecology, Seoul National University, Seoul, Republic of Korea.
Biochim Biophys Acta Mol Basis Dis. 2024 Oct;1870(7):167436. doi: 10.1016/j.bbadis.2024.167436. Epub 2024 Jul 25.
Dendritic cells (DCs) undergo glycolytic reprogramming, a metabolic conversion process essential for their activation. Vitamin D has been reported to affect the function of DCs, but studies in metabolic diseases are insufficient. This study investigates the effects of in vitro 1,25-dihydroxyvitamin D3 (1,25(OH)D) treatment on glycolytic reprogramming of bone marrow-derived dendritic cells (BMDCs) from control, obese, and atherosclerosis mice. Six-week-old male C57BL/6J mice were fed a control diet (CON) or a Western diet (WD), and B6.129S7-Ldlr/J mice were fed a Western diet (LDLR) for 16 weeks. BMDCs were cultured in a medium containing 1,25(OH)D (10 nM) for 7 days and stimulated with lipopolysaccharide (LPS, 50 ng/mL) for 24 h. In mature BMDCs, 1,25(OH)D treatment decreased basal and compensatory glycolytic proton efflux rates (glycoPER), the expression of surface markers related to immune function of DCs (MHC class II, CD80, and CD86), and IL-12p70 production. In addition, mTORC1 activation and nitric oxide (NO) production were suppressed by 1,25(OH)D treatment in mature BMDCs. The effect of 1,25(OH)D treatment on IL-12p70 production and mTORC1 activity in the LDLR group was greater than in the CON group. These findings suggest that vitamin D can affect the metabolic environment of BMDCs by regulating glycolytic reprogramming as well as by inducing tolerogenic phenotypes of DCs.
树突状细胞（DCs）经历糖酵解重编程，这是一种对其激活至关重要的代谢转换过程。维生素 D 已被报道影响 DCs 的功能，但在代谢性疾病中的研究还不够充分。本研究调查了体外 1,25-二羟维生素 D3（1,25(OH)D）处理对来自对照、肥胖和动脉粥样硬化小鼠的骨髓来源树突状细胞（BMDCs）糖酵解重编程的影响。将 6 周龄雄性 C57BL/6J 小鼠喂食对照饮食（CON）或西方饮食（WD），并将 B6.129S7-Ldlr/J 小鼠喂食西方饮食（LDLR）16 周。将 BMDCs 在含有 1,25(OH)D（10 nM）的培养基中培养 7 天，并以脂多糖（LPS，50 ng/mL）刺激 24 小时。在成熟的 BMDCs 中，1,25(OH)D 处理降低了基础和补偿性糖酵解质子外排率（glycoPER）、与 DC 免疫功能相关的表面标志物（MHC 类 II、CD80 和 CD86）的表达以及 IL-12p70 的产生。此外，1,25(OH)D 处理抑制了成熟 BMDCs 中 mTORC1 的激活和一氧化氮（NO）的产生。与 CON 组相比，1,25(OH)D 处理对 LDLR 组中 IL-12p70 产生和 mTORC1 活性的影响更大。这些发现表明，维生素 D 可以通过调节糖酵解重编程以及诱导 DC 的耐受表型来影响 BMDCs 的代谢环境。
