Inhibition of succinate dehydrogenase activity impairs human T cell activation and function: [Publisher correction]

Claudia Nastasi, Andreas Willerlev-Olsen, Kristoffer Dalhoff, Shayne L. Ford, Anne Sofie Østergaard Gadsbøll, Terkild Brink Buus, Maria Gluud, Morten Danielsen, Thomas Litman, Charlotte Mennè Bonefeld, Carsten Geisler, Niels Ødum, Anders Woetmann*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

30 Citations (Scopus)
72 Downloads (Pure)

Abstract

T cell activation is intimately linked to metabolism, as distinct metabolic requirements support the functional and phenotypical differences between quiescent and activated T cells. Metabolic transition from mitochondrial oxidative phosphorylation to aerobic glycolysis is crucial for a proper T cell activation. However, the role of tricarboxylic acid cycle (TCA), and in particular succinate dehydrogenase (SDH) in activated T cells needs further elucidation. Here we show that inhibition of SDH during activation of T cells results in strong impairment of proliferation, expression of activation markers, and production of key inflammatory cytokines, despite a concomitant increase in glycolytic metabolic activity. Similar effect of SDH inhibition were demonstrated in pre-activated T cell. Interestingly, itaconic acid, an endogenous SDH inhibitor released from activated macrophages and dendritic cells, had no immunomodulator effect. Taken together, our findings demonstrate that SDH enzyme fitness is critical for mounting and maintaining appropriate activation and function of human T cells.

Original languageEnglish
Article number1458
JournalScientific Reports
Volume11
Issue number1
ISSN2045-2322
DOIs
Publication statusPublished - 2021

Bibliographical note

Publisher Correction: https://www.nature.com/articles/s41598-021-88184-w
DOI: 10.1038/s41598-021-88184-w

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