Tolerogenic effects of 1,25-dihydroxyvitamin D on dendritic cells involve induction of fatty acid synthesis

Research output: Contribution to journalArticlepeer-review

Authors

External organisations

  • Universität Leipzig
  • Maastricht University
  • Institute of Metabolism and Systems Research (IMSR)
  • University of Maastricht, Maastricht Medical Center, Maastricht, the Netherlands

Abstract

The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) is a potent regulator of immune function, promoting anti-inflammatory, tolerogenic T cell responses by modulating antigen presentation by dendritic cells (DC). Transcriptomic analyses indicate that DC responses to 1,25D involve changes in glycolysis, oxidative phosphorylation, electron transport and the TCA cycle. To determine the functional impact of 1,25D-mediated metabolic remodelling, human monocyte-derived DC were differentiated to immature (+vehicle, iDC), mature (+LPS, mDC), and immature tolerogenic DC (+1,25D, itolDC) and characterised for metabolic function. In contrast to mDC which showed no change in respiration, itolDC showed increased basal and ATP-linked respiration relative to iDC. Tracer metabolite analyses using 13C -labeled glucose showed increased lactate and TCA cycle metabolites. Analysis of lipophilic metabolites of 13C-glucose revealed significant incorporation of label in palmitate and palmitoleate, indicating that 1,25D promotes metabolic fatty acid synthesis in itolDC. Inhibition of fatty acid synthesis in itolDC altered itolDC morphology and suppressed expression of CD14 and IL-10 by these cells. These data indicate that the ability of 1,25D to induce tolerogenic DC involves metabolic remodelling leading to synthesis of fatty acids.

Bibliographic note

Funding Information: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported AMG was supported by a PhD Studentship from the Maastricht-Birmingham PhD Programme . DL was supported by a PhD studentship from the Medical Research Council . EB was supported by a MIDAS PhD studentship from the Wellcome Trust . MH is supported by a Royal Society Wolfson Merit Award ( WM130118 ) and National Institutes of Health ( AR063910 ). Publisher Copyright: © 2021 The Authors

Details

Original languageEnglish
Article number105891
Number of pages10
JournalThe Journal of Steroid Biochemistry and Molecular Biology
Volume211
Early online date27 Mar 2021
Publication statusE-pub ahead of print - 27 Mar 2021

Keywords

  • Dendritic cell, Fatty acid synthesis, Glycolysis, Metabolism, TCA cycle, Vitamin D