Title: Vitamin D3 Induces Tolerance in Human Dendritic Cells by Activation of Intracellular Metabolic Pathways
Authors: Bomfim Ferreira, Gabriela ×
Vanherwegen, An-Sofie
Eelen, Guy
Gutiérrez, Ana Carolina Fierro
Van Lommel, Leentje
Marchal, Kathleen
Verlinden, Lieve
Verstuyf, Annemieke
Nogueira, Tatiane Cristina
Georgiadou, Maria
Schuit, Frans
Eizirik, Décio L
Gysemans, Conny
Carmeliet, Peter
Overbergh, Lut
Mathieu, Chantal #
Issue Date: Feb-2015
Publisher: Elsevier Inc
Series Title: Cell Reports vol:Ahead of print
Article number: S2211-1247(15)00026-1
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 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.
ISSN: 2211-1247
Publication status: accepted
KU Leuven publication type: IT
Appears in Collections:Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
Clinical and Experimental Endocrinology
Centre of Microbial and Plant Genetics
Gene Expression Unit
× corresponding author
# (joint) last author

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