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S-2-氨酸调节CD8+T淋巴细胞的命运
Petros A Tyrakis1,2, Asis Palazon1, David Macias1
1Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
Nature
|November 8, 2016
概括
作为一种免疫代谢物,S- 2氨酸会在T细胞中积聚并增强其抗瘤活性. 这种代谢物将细胞代谢与免疫细胞功能和表观遗传调节联系起来.
科学领域:
- 免疫代谢
- 表观遗传学
- 细胞代谢
背景情况:
- 通过异酸脱酶突变,R- 2 - 水氧酸盐 (2- HG) 的积累与癌症有关.
- 这两种R-和S-2-酸酶体的生理作用尚不清楚.
- 在健康人群中检测到2- 基酸盐,这表明了潜在的生理相关性.
研究的目的:
- 研究CD8+T细胞中的2-基酸盐的积累和功能.
- 阐明T细胞中2-基酸盐积累的机制.
- 确定S-2-酸对T细胞功能和抗瘤免疫力的影响.
主要方法:
- 在T细胞受体刺激后,对小鼠CD8+T细胞中的2-基酸盐水平进行分析.
- 对低氧诱导的1-α因子 (HIF-1α) 对2-基酸盐积累的依赖性进行研究.
- 对T细胞分化标志物,基因组/DNA脱甲基化和HIF-1α稳定性的S-2-酸影响的评估.
- 在体内对S-2-酸对CD8+T细胞增殖,持久性和抗瘤能力的影响的评估.
主要成果:
- 在依赖HIF- 1α的T细胞受体触发后,2- 基酸盐在小鼠CD8+ T细胞中积聚.
- 在激活的T细胞中,S- 2基酸盐占主导地位,并改变CD8+T细胞分化标志物.
- S- 2基酸盐调节基因组和DNA脱甲基化,并影响HIF- 1α的稳定性.
- 用S- 2氨酸治疗显著增强了CD8+ T细胞的体内抗瘤功能.
结论:
- 在CD8+T细胞中,S-2-基酸作为一个关键的免疫代谢物.
- 这种代谢物通过代谢-表观遗传轴连接环境线索与免疫细胞命运.
- 增强T细胞增殖,持久性和抗瘤功效,具有治疗潜力.
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