Garcia 2021 J Steroid Biochem Mol Biol

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Garcia AM, Bishop EL, Li D, Jeffery LE, Garten A, Thakker A, Certo M, Mauro C, Tennant DA, Dimeloe S, Evelo CT, Coort SL, Hewison M (2021) Tolerogenic effects of 1,25-dihydroxyvitamin D on dendritic cells involve induction of fatty acid synthesis. J Steroid Biochem Mol Biol 211:105891.

Β» PMID: 33785437 Open Access

Garcia Amadeo Munoz, Bishop Emma L, Li Danyang, Jeffery Louisa E, Garten Antje, Thakker Alpesh, Certo Michelangelo, Mauro Claudio, Tennant Daniel A, Dimeloe Sarah, Evelo Chris T, Coort Susan L, Hewison Martin (2021) J Steroid Biochem Mol Biol

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. β€’ Keywords: Dendritic cell, Fatty acid synthesis, Glycolysis, Metabolism, TCA cycle, Vitamin D β€’ Bioblast editor: Plangger M, Reiswig R

Labels: MiParea: Respiration, Pharmacology;toxicology 

Organism: Human  Tissue;cell: Blood cells  Preparation: Intact cells  Enzyme: TCA cycle and matrix dehydrogenases 

Coupling state: LEAK, ROUTINE, ET  Pathway: ROX  HRR: Oxygraph-2k 

2021-07, PBMC 

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