期刊
CELL REPORTS
卷 10, 期 5, 页码 711-725出版社
CELL PRESS
DOI: 10.1016/j.celrep.2015.01.013
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资金
- Flemish Research Foundation [G.0649.08, G.0734.10]
- Belgium Program on Interuniversity Poles of Attraction initiated by the Belgian State [P6/40]
- Katholieke Universiteit Leuven [GOA 2009/10, GOA 14/010]
- 7th Framework Program of the European Union (NAIMIT)
Metabolic switches in various immune cell subsets enforce phenotype and function. In the present study, we demonstrate that the active form of vitamin D, 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3), induces human monocyte-derived tolerogenic dendritic cells (DC) by metabolic reprogramming. Microarray analysis demonstrated that 1,25(OH)(2)D-3 upregulated several genes directly related to glucose metabolism, tricarboxylic acid cycle (TCA), and oxidative phosphorylation (OXPHOS). Although OXPHOS was promoted by 1,25(OH)(2)D-3, hypoxia did not change the tolerogenic function of 1,25(OH)(2)D-3-treated DCs. Instead, glucose availability and glycolysis, controlled by the PI3K/Akt/mTOR pathway, dictate the induction and maintenance of the 1,25(OH)(2)D(3)conditioned tolerogenic DC phenotype and function. This metabolic reprogramming is unique for 1,25(OH)(2)D-3, because the tolerogenic DC phenotype induced by other immune modulators did not depend on similar metabolic changes. We put forward that these metabolic insights in tolerogenic DC biology can be used to advance DC-based immunotherapies, influencing DC longevity and their resistance to environmental metabolic stress.
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