过度表达AMPKγ2会增加AMPK信号,以增强人类T细胞的新陈代谢和功能
Erica L Braverman1, Margaret A McQuaid1, Herbert Schuler1
1Division of Blood and Marrow Transplant and Cellular Therapies, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
The Journal of biological chemistry
|November 24, 2023
概括
增强人类T细胞中AMP激活蛋白激酶 (AMPK) 信号传递,提高了它们的代谢适应性和线粒体功能. 这改善了T细胞的增殖和细胞因子的产生,使它们更有效的采用细胞疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 代谢工程是代谢工程.
背景情况:
- T细胞疗法需要代谢适合的细胞,以获得最佳的体内疗效.
- AMP激活蛋白激酶 (AMPK) 是一个关键的细胞能量传感器,调节代谢编程.
- 增强AMPK活性可以改善T细胞功能,用于治疗应用.
研究的目的:
- 调查是否增加人类T细胞中的AMPK活性增加了它们的氧化能力.
- 确定增强的AMPK信号对T细胞增殖,细胞因子产生和功能的影响.
- 评估AMPKγ2过度表达在采用细胞疗法中改善T细胞的潜力.
主要方法:
- 使用lentiviral转导来过度表达人类T细胞中的AMPKγ2亚单元.
- 通过测量氧气消耗率 (基础,最大,备用容量) 来评估线粒体呼吸.
- 评估了T细胞增殖,炎症性细胞因子生产 (IL-4,IL-5) 和调控性T细胞抑制能力.
主要成果:
- 过度表达AMPKγ2增强了内在的AMPK信号传递,并促进了线粒体呼吸.
- 观察到基底和最大氧气消耗率的增加以及增加的备用呼吸能力.
- AMPKγ2增强了T细胞增殖和炎症性细胞因子的产生,特别是在低葡萄糖条件下,并改善了调节性T细胞功能.
结论:
- 通过AMPKγ2过度表达来增加内在AMPK信号,可以改善人类T细胞的代谢适应性和功能.
- 增强的T细胞表现出增加的增殖,细胞因子的产生,并改善了调节性T细胞的抑制能力.
- 这一策略有望提高基于T细胞的采用细胞疗法的疗效.
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