Glutathione Primes T Cell Metabolism for Inflammation

Tak W. Mak*, Melanie Grusdat, Gordon S. Duncan, Catherine Dostert, Yannic Nonnenmacher, Maureen Cox, Carole Binsfeld, Zhenyue Hao, Anne Brüstle, Momoe Itsumi, Christian Jäger, Ying Chen, Olaf Pinkenburg, Bärbel Camara, Markus Ollert, Carsten Bindslev-Jensen, Vasilis Vasiliou, Chiara Gorrini, Philipp A. Lang, Michael LohoffIsaac S. Harris, Karsten Hiller, Dirk Brenner

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

289 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)675-689
Number of pages15
Issue number4
Publication statusPublished - 18 Apr 2017


  • GSH
  • Gclc
  • Myc
  • NFAT
  • ROS
  • T cells
  • glutathione
  • glycolysis
  • mTOR
  • metabolic reprogramming
  • metabolism
  • reactive oxygen species


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