The two enantiomers of 2-hydroxyglutarate differentially regulate cytotoxic T cell function

Iosifina P. Foskolou; Pedro P. Cunha; Elena Sanchez-Lopez; Eleanor A. Minogue; Beno P. Nicolet; Aurelie Guislain; Christian Jorgensen; Sarantos Kostidis; Nordin D. Zandhuis; Laura Barbieri; David Bargiela; Demitris Nathanael; Petros A. Tyrakis; Asis Palazon; Martin Giera; Monika C. Wolkers; Randall S. Johnson

doi:10.1016/j.celrep.2023.113013

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The two enantiomers of 2-hydroxyglutarate differentially regulate cytotoxic T cell function

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The two enantiomers of 2-hydroxyglutarate differentially regulate cytotoxic T cell function

Iosifina P. Foskolou, Pedro P. Cunha, Elena Sanchez-Lopez, Eleanor A. Minogue, Beno P. Nicolet, Aurelie Guislain, Christian Jorgensen, Sarantos Kostidis, Nordin D. Zandhuis, Laura Barbieri, …

Cell reports (Cambridge), Vol.42(9), p.113013

26/09/2023

DOI: https://doi.org/10.1016/j.celrep.2023.113013

PMID: 37632752

Résumé

Cell Biology

Life Sciences & Biomedicine

Science & Technology

2-Hydroxyglutarate (2HG) is a byproduct of the tricarboxylic acid (TCA) cycle and is readily detected in the tissues of healthy individuals. 2HG is found in two enantiomeric forms: S-2HG and R-2HG. Here, we investigate the differential roles of these two enantiomers in cluster of differentiation (CD)8+ T cell biology, where we find they have highly divergent effects on proliferation, differentiation, and T cell function. We show here an analysis of structural determinants that likely underlie these differential effects on specific a-ketoglutarate (aKG)-dependent enzymes. Treatment of CD8+ T cells with exogenous S-2HG, but not R-2HG, increased CD8+ T cell fitness in vivo and enhanced anti-tumor activity. These data show that S-2HG and R-2HG should be considered as two distinct and important actors in the regulation of T cell function.

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Titre: The two enantiomers of 2-hydroxyglutarate differentially regulate cytotoxic T cell function
Créateurs - sans rôle: Iosifina P. Foskolou - Univ Cambridge, Dept Physiol Dev & Neurosci, Downing Site, Cambridge CB2 3EG, England
Pedro P. Cunha - Univ Cambridge, Dept Physiol Dev & Neurosci, Downing Site, Cambridge CB2 3EG, England
Elena Sanchez-Lopez - Leiden Univ Med Ctr, Ctr Prote & Metabol, Albinusdreef 2, NL-2333ZA Leiden, Netherlands
Eleanor A. Minogue - Univ Cambridge, Dept Physiol Dev & Neurosci, Downing Site, Cambridge CB2 3EG, England
Beno P. Nicolet - Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Hematopoiesis, Sanquin Res & Landsteiner Lab, NL-1066 CX Amsterdam, Netherlands
Aurelie Guislain - Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Hematopoiesis, Sanquin Res & Landsteiner Lab, NL-1066 CX Amsterdam, Netherlands
Christian Jorgensen - Aarhus Univ, Dept Chem, Langelandsgade 140, DK-8000 Aarhus, Denmark
Sarantos Kostidis - Leiden Univ Med Ctr, Ctr Prote & Metabol, Albinusdreef 2, NL-2333ZA Leiden, Netherlands
Nordin D. Zandhuis - Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Hematopoiesis, Sanquin Res & Landsteiner Lab, NL-1066 CX Amsterdam, Netherlands
Laura Barbieri - Univ Cambridge, Dept Physiol Dev & Neurosci, Downing Site, Cambridge CB2 3EG, England
David Bargiela - Univ Cambridge, Dept Physiol Dev & Neurosci, Downing Site, Cambridge CB2 3EG, England
Demitris Nathanael - Univ Cambridge, Dept Physiol Dev & Neurosci, Downing Site, Cambridge CB2 3EG, England
Petros A. Tyrakis - Univ Cambridge, Dept Physiol Dev & Neurosci, Downing Site, Cambridge CB2 3EG, England
Asis Palazon - Univ Cambridge, Dept Physiol Dev & Neurosci, Downing Site, Cambridge CB2 3EG, England
Martin Giera - Leiden Univ Med Ctr, Ctr Prote & Metabol, Albinusdreef 2, NL-2333ZA Leiden, Netherlands
Monika C. Wolkers - Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Hematopoiesis, Sanquin Res & Landsteiner Lab, NL-1066 CX Amsterdam, Netherlands
Randall S. Johnson - Univ Cambridge, Dept Physiol Dev & Neurosci, Downing Site, Cambridge CB2 3EG, England
Détails de publication: Cell reports (Cambridge), Vol.42(9), p.113013
Éditeur: Elsevier
Nombre de pages: 23
Note de subvention: PR2020-007 / Swedish Children's Cancer Fund (Barncancerfonden) Knut and Alice Wallenberg Scholar Award 2019-01485 / Swedish Research Council Apollo Therapeutics 2019-01485 / Swedish Medical Research Council (Vetenskapsrdet) Evelyn Trust Cambridge CAN2018/808 / Swedish Cancer Fund (Cancer fonden) 214283/Z/18/Z / Wellcome Trust Principal Fellowship Award; Wellcome Trust 2019-01485 / Forte; Swedish Research Council for Health Working Life & Welfare (Forte) SFRH/BD/115612/2016 / Foundation for Science and Technology of Portugal (FCT) scholarship
Identifiants: 99141081209311
Unité académique: Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Langue: English
Type de ressource: Journal article