Inhibition of succinate dehydrogenase activity impairs human T cell activation and function: [Publisher correction]
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Inhibition of succinate dehydrogenase activity impairs human T cell activation and function : [Publisher correction]. / Nastasi, Claudia; Willerlev-Olsen, Andreas; Dalhoff, Kristoffer; Ford, Shayne L.; Gadsbøll, Anne Sofie Østergaard; Buus, Terkild Brink; Gluud, Maria; Danielsen, Morten; Litman, Thomas; Bonefeld, Charlotte Mennè; Geisler, Carsten; Ødum, Niels; Woetmann, Anders.
In: Scientific Reports, Vol. 11, No. 1, 1458, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Inhibition of succinate dehydrogenase activity impairs human T cell activation and function
T2 - [Publisher correction]
AU - Nastasi, Claudia
AU - Willerlev-Olsen, Andreas
AU - Dalhoff, Kristoffer
AU - Ford, Shayne L.
AU - Gadsbøll, Anne Sofie Østergaard
AU - Buus, Terkild Brink
AU - Gluud, Maria
AU - Danielsen, Morten
AU - Litman, Thomas
AU - Bonefeld, Charlotte Mennè
AU - Geisler, Carsten
AU - Ødum, Niels
AU - Woetmann, Anders
N1 - Publisher Correction: https://www.nature.com/articles/s41598-021-88184-w DOI: 10.1038/s41598-021-88184-w
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
UR - https://www.nature.com/articles/s41598-021-88184-w
U2 - 10.1038/s41598-020-80933-7
DO - 10.1038/s41598-020-80933-7
M3 - Journal article
C2 - 33446766
AN - SCOPUS:85099437262
VL - 11
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 1458
ER -
ID: 255683674