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Vitamin D3 induces tolerance in human dendritic cells by activation of intracellular metabolic pathways

(2015) CELL REPORTS. 10(5). p.711-725
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Bioinformatics: from nucleotids to networks (N2N)
Abstract
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.
Keywords
AUTOREACTIVE T-CELLS, ANTIGEN, D-RECEPTOR, 1_25-DIHYDROXYVITAMIN D-3, INDUCTION, GROWTH, DIFFERENTIATION, REGULATOR, HYPOXIA, COMPLEX, IBCN

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Citation

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Chicago
Ferreira, Gabriela Bomfim, An-Sofie Vanherwegen, Guy Eelen, Ana Carolina Fierro Gutíerrez, Leentje Van Lommel, Kathleen Marchal, Lieve Verlinden, et al. 2015. “Vitamin D3 Induces Tolerance in Human Dendritic Cells by Activation of Intracellular Metabolic Pathways.” Cell Reports 10 (5): 711–725.
APA
Ferreira, G. B., Vanherwegen, A.-S., Eelen, G., Gutíerrez, A. C. F., Van Lommel, L., Marchal, K., Verlinden, L., et al. (2015). Vitamin D3 induces tolerance in human dendritic cells by activation of intracellular metabolic pathways. CELL REPORTS, 10(5), 711–725.
Vancouver
1.
Ferreira GB, Vanherwegen A-S, Eelen G, Gutíerrez ACF, Van Lommel L, Marchal K, et al. Vitamin D3 induces tolerance in human dendritic cells by activation of intracellular metabolic pathways. CELL REPORTS. 2015;10(5):711–25.
MLA
Ferreira, Gabriela Bomfim, An-Sofie Vanherwegen, Guy Eelen, et al. “Vitamin D3 Induces Tolerance in Human Dendritic Cells by Activation of Intracellular Metabolic Pathways.” CELL REPORTS 10.5 (2015): 711–725. Print.
@article{5945315,
  abstract     = {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.},
  author       = {Ferreira, Gabriela Bomfim and Vanherwegen, An-Sofie and Eelen, Guy and Gut{\'i}errez, Ana Carolina Fierro and Van Lommel, Leentje and Marchal, Kathleen and Verlinden, Lieve and Verstuyf, Annemieke and Nogueira, Tatiane and Georgiadou, Maria and Schuit, Frans and Eizirik, D{\'e}cio L and Gysemans, Conny and Carmeliet, Peter and Overbergh, Lut and Mathieu, Chantal},
  issn         = {2211-1247},
  journal      = {CELL REPORTS},
  keyword      = {AUTOREACTIVE T-CELLS,ANTIGEN,D-RECEPTOR,1\_25-DIHYDROXYVITAMIN D-3,INDUCTION,GROWTH,DIFFERENTIATION,REGULATOR,HYPOXIA,COMPLEX,IBCN},
  language     = {eng},
  number       = {5},
  pages        = {711--725},
  title        = {Vitamin D3 induces tolerance in human dendritic cells by activation of intracellular metabolic pathways},
  url          = {http://dx.doi.org/10.1016/j.celrep.2015.01.013},
  volume       = {10},
  year         = {2015},
}

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