通过有氧糖溶解对T细胞效应因子功能的转录后控制
Chih-Hao Chang1, Jonathan D Curtis, Leonard B Maggi
1Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell
|June 11, 2013
概括
细胞使用有氧糖解不是用于增殖,而是用于效应器功能,如IFN-γ生产. 这种代谢开关由GAPDH与IFN-γmRNA结合来调节,控制细胞因子的产生.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞的新陈代谢
- 分子生物学分子生物学
背景情况:
- T细胞激活通常涉及从氧化酸化 (OXPHOS) 到有氧糖解的代谢转变.
- 这种新陈代谢重编程传统上与满足细胞增殖的高能量需求有关.
- 有氧糖解在T细胞功能中的确切作用和必要性,特别是在富含氧气的条件下,仍然不清楚.
研究的目的:
- 调查有氧糖解在T细胞激活,增殖和效应器功能中的特定作用.
- 确定有氧糖解是否对T细胞生存和增殖至关重要.
- 阐明有氧糖解影响T细胞效应器功能的分子机制,例如细胞因子生产.
主要方法:
- 使用了具有或没有糖解抑制的活性T细胞.
- 评估T细胞的增殖,生存和效应器功能,包括IFN-γ的产生.
- 研究了IFN-γmRNA的翻译调节,通过检查糖-3-酸脱酶 (GAPDH) 与AU丰富元素结合的作用.
主要成果:
- 有氧糖解对于T细胞的效应器功能至关重要,特别是对于IFN-γ的产生,但不是为了增殖或生存.
- 抑制糖解会显著影响激活的T细胞产生IFN-γ的能力.
- 糖解酶GAPDH被确定为一个关键的调节器,与IFN-γ mRNA的3' UTR结合,以控制其翻译,从而影响细胞因子的产生.
结论:
- 有氧糖解作为T细胞的关键信号机制,主要调节效应器功能,而不是增殖.
- 代谢酶GAPDH在通过IFN-γmRNA的转录后调节来控制T细胞效应因子细胞因子的产生中起着至关重要的作用.
- 这项研究重新定义了有氧糖解在T细胞激活中的作用,强调了其作为细胞信号和效应因子反应代谢调节者的功能.
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