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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Vitamin D3 induces tolerance in human dendritic cells by activation of intracellular metabolic pathways
Cell Reports, Volume 10, No. 5, Year 2015
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Description
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 D3 (1,25(OH)2D3), induces human monocyte-derived tolerogenic dendritic cells (DC) by metabolic reprogramming. Microarray analysis demonstrated that 1,25(OH)2D3 upregulated several genes directly related to glucose metabolism, tricarboxylic acid cycle (TCA), and oxidative phosphorylation (OXPHOS). Although OXPHOS was promoted by 1,25(OH)2D3, hypoxia did not change the tolerogenic function of 1,25(OH)2D3-treated DCs. Instead, glucose availability and glycolysis, controlled by the PI3K/Akt/mTOR pathway, dictate the induction and maintenance of the 1,25(OH)2D3-conditioned tolerogenic DC phenotype and function.This metabolic reprogramming is unique for 1,25(OH)2D3, 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. © 2015 The Authors.
Authors & Co-Authors
Eelen, Guy
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Marchal, Kathleen
Belgium, Leuven
Ku Leuven
Belgium, Ghent
Universiteit Gent
Carmeliet, Peter F.M.
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Overbergh, Lut
Belgium, Leuven
Ku Leuven
Mathieu, Chantal
Belgium, Leuven
Ku Leuven
Statistics
Citations: 201
Authors: 5
Affiliations: 4
Identifiers
Doi:
10.1016/j.celrep.2015.01.013
ISSN:
22111247
Research Areas
Noncommunicable Diseases