Lee Jang Eun, Walsh Matthew C, Hoehn Kyle L, James David E, Wherry E John, Choi Yongwon
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, United States of America; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, United States of America.
Department of Pharmacology, University of Virginia Health System, Charlottesville, Virginia, 22908, United States of America.
PLoS One. 2015 Sep 14;10(9):e0137776. doi: 10.1371/journal.pone.0137776. eCollection 2015.
Differentiation of T cells is closely associated with dynamic changes in nutrient and energy metabolism. However, the extent to which specific metabolic pathways and molecular components are determinative of CD8+ T cell fate remains unclear. It has been previously established in various tissues that acetyl CoA carboxylase 2 (ACC2) regulates fatty acid oxidation (FAO) by inhibiting carnitine palmitoyltransferase 1 (CPT1), a rate-limiting enzyme of FAO in mitochondria. Here, we explore the cell-intrinsic role of ACC2 in T cell immunity in response to infections. We report here that ACC2 deficiency results in a marginal increase of cellular FAO in CD8+ T cells, but does not appear to influence antigen-specific effector and memory CD8+ T cell responses during infection with listeria or lymphocytic choriomeningitis virus. These results suggest that ACC2 is dispensable for CD8+ T cell responses.
T细胞的分化与营养和能量代谢的动态变化密切相关。然而,特定代谢途径和分子成分在多大程度上决定CD8+T细胞命运仍不清楚。此前在各种组织中已证实,乙酰辅酶A羧化酶2(ACC2)通过抑制肉碱棕榈酰转移酶1(CPT1)来调节脂肪酸氧化(FAO),CPT1是线粒体中FAO的限速酶。在此,我们探讨ACC2在T细胞免疫应答感染中的细胞内在作用。我们在此报告,ACC2缺陷导致CD8+T细胞中细胞FAO略有增加,但在感染李斯特菌或淋巴细胞性脉络丛脑膜炎病毒期间,似乎不影响抗原特异性效应和记忆CD8+T细胞反应。这些结果表明,ACC2对于CD8+T细胞反应是可有可无的。