Reference : Glutathione Primes T Cell Metabolism for Inflammation
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
Glutathione Primes T Cell Metabolism for Inflammation
Mak, Tak W. [> >]
Grusdat, Melanie [> >]
Duncan, Gordon S. [> >]
Dostert, Catherine [> >]
Nonnenmacher, Yannic [> >]
Cox, Maureen [> >]
Binsfeld, Carole [> >]
Hao, Zhenyue [> >]
Brüstle, Anne [> >]
Itsumi, Momoe [> >]
Jäger, Christian mailto [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. [> >]
Hiller, Karsten []
Brenner, Dirk [> >]
Yes (verified by ORBilu)
[en] metabolic reprogramming ; metabolism ; glycolysis ; glutathione ; GSH ; Gclc ; reactive oxygen species ; ROS ; NFAT ; mTOR ; Myc ; T cells
[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.

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