| First Author | Mak TW | Year | 2017 |
| Journal | Immunity | Volume | 46 |
| Issue | 4 | Pages | 675-689 |
| PubMed ID | 28423341 | Mgi Jnum | J:259281 |
| Mgi Id | MGI:6140740 | Doi | 10.1016/j.immuni.2017.03.019 |
| Citation | Mak TW, et al. (2017) Glutathione Primes T Cell Metabolism for Inflammation. Immunity 46(4):675-689 |
| abstractText | 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. |
