Article (Scientific journals)
Glutathione Primes T Cell Metabolism for Inflammation
Mak, Tak W.; Grusdat, Melanie; Duncan, Gordon S. et al.
2017In Immunity, 46 (4), p. 675-689
Peer reviewed
 

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Keywords :
metabolic reprogramming; metabolism; glycolysis; glutathione; GSH; Gclc; reactive oxygen species; ROS; NFAT; mTOR; Myc; T cells
Abstract :
[en] Activated T cells produce reactive oxygen species (ROS), which trigger the antioxidative glutathione (GSH) response necessary to buffer rising ROS and prevent cellular damage. We report that GSH is essential for T cell effector functions through its regulation of metabolic activity. Conditional gene targeting of the catalytic subunit of glutamate cysteine ligase (Gclc) blocked GSH production specifically in murine T cells. Gclc-deficient T cells initially underwent normal activation but could not meet their increased energy and biosynthetic requirements. GSH deficiency compromised the activation of mammalian target of rapamycin-1 (mTOR) and expression of NFAT and Myc transcription factors, abrogating the energy utilization and Myc-dependent metabolic reprogramming that allows activated T cells to switch to glycolysis and glutaminolysis. In vivo, T-cell-specific ablation of murine Gclc prevented autoimmune disease but blocked antiviral defense. The antioxidative GSH pathway thus plays an unexpected role in metabolic integration and reprogramming during inflammatory T cell responses.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Mak, Tak W.
Grusdat, Melanie
Duncan, Gordon S.
Dostert, Catherine
Nonnenmacher, Yannic
Cox, Maureen
Binsfeld, Carole
Hao, Zhenyue
Brüstle, Anne
Itsumi, Momoe
Jäger, Christian  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Chen, Ying
Pinkenburg, Olaf
Camara, Bärbel
Ollert, Markus
Bindslev-Jensen, Carsten
Vasiliou, Vasilis
Gorrini, Chiara
Lang, Philipp A.
Lohoff, Michael
Harris, Isaac S.
Brenner, Dirk
More authors (13 more) Less
External co-authors :
yes
Language :
English
Title :
Glutathione Primes T Cell Metabolism for Inflammation
Publication date :
18 April 2017
Journal title :
Immunity
ISSN :
1074-7613
Volume :
46
Issue :
4
Pages :
675-689
Peer reviewed :
Peer reviewed
Focus Area :
Systems Biomedicine
Available on ORBilu :
since 19 September 2017

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