ACLY和ACSS2将依赖营养素的染色质可访问性与CD8 T细胞效应因子反应联系起来
Irem Kaymak1, McLane J Watson1, Brandon M Oswald1
1Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.
The Journal of experimental medicine
|August 16, 2024
概括
细胞酸乙-CoA的产生对CD8 T细胞功能至关重要. 酸酸酶 (ACLY) 和酸-CoA合成酶 (ACSS2) 协调这一过程,确保T细胞效应因子反应和染色质可访问性.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞的新陈代谢
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 细胞代谢协调对于有效的T细胞反应至关重要.
- 细胞酸乙-CoA是一种关键的代谢中间体,影响细胞功能.
研究的目的:
- 在体内确定CD8T细胞功能的关键代谢途径.
- 阐明ATP酸酶 (ACLY) 和短链乙-CoA合成酶家族成员2 (ACSS2) 在CD8 T细胞代谢中的作用.
主要方法:
- 在体内研究了 CD8 T 细胞对感染的反应.
- 利用ACLY的遗传切除来研究替代代代谢途径.
- 分析了乙酸代谢对T细胞效应因子功能和基因素乙化的影响.
主要成果:
- CD8 T细胞对感染的反应依赖于由ACLY产生的乙-CoA.
- 丢失ACLY激活了通过ACSS2产生乙-CoA的另一种依赖乙酸盐的途径.
- 乙酸为TCA循环和细胞酸乙-CoA提供燃料,影响T细胞效应反应和染色质可访问性.
结论:
- ACLY 和 ACSS2 是 CD8 T 细胞中细胞酸乙-CoA 生产的关键调节剂.
- 这种代谢协调对于维持染色质可访问性和T细胞效应器功能至关重要.
- 虽然不是强制性的,但当ACLY是非功能性的时,通过ACSS2进行酸盐代谢变得至关重要.
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