2-羟基戊二酸的两个同分异构体对细胞毒性T细胞功能的调节存在差异。
The two enantiomers of 2-hydroxyglutarate differentially regulate cytotoxic T cell function.
发表日期：2023 Aug 24
作者：
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
来源：
Cell Reports
摘要：
2-羟基戊二酸酯 (2HG) 是三羧酸循环 (TCA) 的副产物，可在健康个体的组织中被快速检测到。2HG以两种旋光异构体的形式存在：S-2HG和R-2HG。在这里，我们探讨了这两种异构体在CD8+T细胞生物学中的差异作用，发现它们对增殖、分化和T细胞功能具有高度差异的影响。我们在这里展示了对可能潜在地解释这些差异效应的特定α-酮戊二酸 (αKG) 依赖酶的结构确定者的分析。用外源的S-2HG处理CD8+T细胞，但不是R-2HG，增加了树突状突触的树突突触形态和增加了抗肿瘤活性。这些数据表明S-2HG和R-2HG应被视为T细胞功能调节中两个独立而重要的角色。
© 2023版权所有 Elsevier Inc. 发行
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.Copyright © 2023. Published by Elsevier Inc.