Vitamin D3 induces tolerance in human dendritic cells by activation of intracellular metabolic pathways
- Author
- Gabriela Bomfim Ferreira, An-Sofie Vanherwegen, Guy Eelen, Ana Carolina Fierro Gutíerrez, Leentje Van Lommel, Kathleen Marchal (UGent) , Lieve Verlinden, Annemieke Verstuyf, Tatiane Nogueira, Maria Georgiadou, Frans Schuit, Décio L Eizirik, Conny Gysemans, Peter Carmeliet, Lut Overbergh and Chantal Mathieu
- Organization
- Project
- 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
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-5945315
- MLA
- Ferreira, Gabriela Bomfim, et al. “Vitamin D3 Induces Tolerance in Human Dendritic Cells by Activation of Intracellular Metabolic Pathways.” CELL REPORTS, vol. 10, no. 5, 2015, pp. 711–25, doi:10.1016/j.celrep.2015.01.013.
- APA
- Ferreira, G. B., Vanherwegen, A.-S., Eelen, G., Gutíerrez, A. C. F., Van Lommel, L., Marchal, K., … Mathieu, C. (2015). Vitamin D3 induces tolerance in human dendritic cells by activation of intracellular metabolic pathways. CELL REPORTS, 10(5), 711–725. https://doi.org/10.1016/j.celrep.2015.01.013
- Chicago author-date
- 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): 711–25. https://doi.org/10.1016/j.celrep.2015.01.013.
- Chicago author-date (all authors)
- Ferreira, Gabriela Bomfim, An-Sofie Vanherwegen, Guy Eelen, Ana Carolina Fierro Gutíerrez, Leentje Van Lommel, Kathleen Marchal, Lieve Verlinden, Annemieke Verstuyf, Tatiane Nogueira, Maria Georgiadou, Frans Schuit, Décio L Eizirik, Conny Gysemans, Peter Carmeliet, Lut Overbergh, and Chantal Mathieu. 2015. “Vitamin D3 Induces Tolerance in Human Dendritic Cells by Activation of Intracellular Metabolic Pathways.” CELL REPORTS 10 (5): 711–725. doi:10.1016/j.celrep.2015.01.013.
- 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.
- IEEE
- [1]G. B. Ferreira et al., “Vitamin D3 induces tolerance in human dendritic cells by activation of intracellular metabolic pathways,” CELL REPORTS, vol. 10, no. 5, pp. 711–725, 2015.
@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 Gutíerrez, 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, Décio L and Gysemans, Conny and Carmeliet, Peter and Overbergh, Lut and Mathieu, Chantal}},
issn = {{2211-1247}},
journal = {{CELL REPORTS}},
keywords = {{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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