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

2021; Elsevier BV; Volume: 211; Linguagem: Inglês

10.1016/j.jsbmb.2021.105891

1879-1220

Amadeo Muñoz García, Emma L. Bishop, Danyang Li, Louisa Jeffery, Antje Garten, Alpesh Thakker, Michelangelo Certo, Claudio Mauro, Daniel A. Tennant, Sarah Dimeloe, Chris T. Evelo, Susan L. Coort, Martin Hewison,

Virus-based gene therapy research

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