dc.contributor.author | Mak, TW | |
dc.contributor.author | Grusdat, M | |
dc.contributor.author | Duncan, GS | |
dc.contributor.author | Dostert, C | |
dc.contributor.author | Nonnenmacher, Y | |
dc.contributor.author | Cox, M | |
dc.contributor.author | Binsfeld, C | |
dc.contributor.author | Hao, Z | |
dc.contributor.author | Brüstle, A | |
dc.contributor.author | Itsumi, M | |
dc.contributor.author | Jäger, C | |
dc.contributor.author | Chen, Y | |
dc.contributor.author | Pinkenburg, O | |
dc.contributor.author | Camara, B | |
dc.contributor.author | Ollert, M | |
dc.contributor.author | Bindslev-Jensen, C | |
dc.contributor.author | Vasiliou, V | |
dc.contributor.author | Gorrini, C | |
dc.contributor.author | Lang, PA | |
dc.contributor.author | Lohoff, M | |
dc.contributor.author | Harris, IS | |
dc.contributor.author | Hiller, K | |
dc.contributor.author | Brenner, D | |
dc.date.accessioned | 2020-09-30T12:51:09Z | |
dc.date.issued | 2017-04-18 | |
dc.identifier.citation | Immunity, 2017, 46 (4), pp. 675 - 689 | |
dc.identifier.issn | 1074-7613 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4099 | |
dc.identifier.eissn | 1097-4180 | |
dc.identifier.doi | 10.1016/j.immuni.2017.03.019 | |
dc.description.abstract | 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. | |
dc.format | Print | |
dc.format.extent | 675 - 689 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.subject | T-Lymphocytes | |
dc.subject | Animals | |
dc.subject | Mice, Inbred C57BL | |
dc.subject | Mice, Knockout | |
dc.subject | Encephalomyelitis, Autoimmune, Experimental | |
dc.subject | Inflammation | |
dc.subject | Reactive Oxygen Species | |
dc.subject | Glutamate-Cysteine Ligase | |
dc.subject | Glutamine | |
dc.subject | Glutathione | |
dc.subject | Proto-Oncogene Proteins c-myc | |
dc.subject | Immunoblotting | |
dc.subject | Signal Transduction | |
dc.subject | Energy Metabolism | |
dc.subject | Glycolysis | |
dc.subject | NFATC Transcription Factors | |
dc.subject | TOR Serine-Threonine Kinases | |
dc.title | Glutathione Primes T Cell Metabolism for Inflammation. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-03-29 | |
rioxxterms.versionofrecord | 10.1016/j.immuni.2017.03.019 | |
rioxxterms.licenseref.startdate | 2017-04 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Immunity | |
pubs.issue | 4 | |
pubs.notes | No embargo | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Target Evaluation and Molecular Therapeutics | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Target Evaluation and Molecular Therapeutics | |
pubs.publication-status | Published | |
pubs.volume | 46 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Target Evaluation and Molecular Therapeutics | |
dc.contributor.icrauthor | Gorrini, Chiara | |