Glutathione primes T cell metabolism for inflammation.

  • Experimental and¬†Molecular Immunology
  • Allergy and Clinical Immunology
April 18, 2017 By:
  • Mak TW
  • Grusdat M
  • Duncan GS
  • Dostert C
  • Nonnenmacher Y
  • Cox M
  • Binsfeld C
  • Hao Z
  • Brustle A
  • Itsumi M
  • Jager C
  • Chen Y
  • Pinkenburg O
  • Camara B
  • Ollert M
  • Bindslev-Jensen C
  • Vasiliou V
  • Gorrini C
  • Lang PA
  • Lohoff M
  • Harris IS
  • Hiller K
  • Brenner D.

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.

2017 Apr. Immunity.46(4):675-689.
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