The two enantiomers of 2-hydroxyglutarate differentially regulate cytotoxic T cell function
Year: 2023
Type: article
Abstract: 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 α-ketoglutarate (αKG)-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.
Source: Cell Reports
Authors: Iosifina P. Foskolou, Pedro P. Cunha, Elena Sánchez-López, Eleanor A. Minogue, Benoît P. Nicolet, Aurélie 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
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,460
Funders: Wellcome Trust, National Institute for Health and Care Research, Cancerfonden, Karolinska Institutet, Evelyn Trust, Vetenskapsrådet, Medicinska Forskningsrådet, Barncancerfonden, Directorate for Biological Sciences, Allos Therapeutics, Medical Research Council, Fundação para a Ciência e a Tecnologia, NIHR Cambridge Biomedical Research Centre
Awards: G1365720483, G1960764132, Título novo: The role of hypoxia in T cell function and immunotherapy. Título inicial: Vascular endothelium: fit for purpose - understanding the molecular basis for organ-specific regulation of vascular (dys)function, G360368086, Oxygen and immune response, G577803821, G6039111964, G6265702644, The physiology of hypoxic response
OpenAlex ID: W4386133628