特定子集的线粒体压力和DNA损伤影响T细胞对发烧和炎症的反应
Darren R Heintzman1, Rachael C Sinard1,2, Emilie L Fisher1
1Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Science immunology
|September 20, 2024
概括
温和的发烧温度可以促进CD4 T细胞功能,但会损害T辅助1 (TH1) 细胞,导致DNA损伤和损害线粒体呼吸. 幸存的TH1细胞适应增强炎症反应.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 热量是炎症的关键信号,但其对免疫细胞的确切影响尚未完全理解.
- 了解温度如何影响T细胞功能对于管理炎症性疾病至关重要.
研究的目的:
- 为了研究发烧范围温度对CD4 T细胞代谢,功能和生存的影响.
- 阐明热量影响不同T辅助细胞子集的特定分子机制,特别是T辅助1 (TH1) 细胞.
主要方法:
- 鼠类CD4 T细胞被暴露在中度发烧温度 (39°C) 中.
- 评估的是细胞代谢,增殖,效应器功能和调节能力.
- 研究了线粒体应激,DNA损伤和关键信号通路的激活 (Trp53,STING).
- 分析了电子运输链复合体1 (ETC1) 功能及其对TH1细胞生存和适应的影响.
- 检查了从慢性炎症中获得的人类样本的相关TH1细胞特征.
主要成果:
- 发烧温度提高了CD4 T细胞代谢,增殖和效应活性,同时降低了调控性T细胞功能.
- 暴露于热量的TH1细胞产生了显著的线粒体应激和DNA损伤,激活了Trp53和STING通路.
- 虽然许多TH1细胞经历了亡,但幸存者显示线粒体质量增加和活性增强.
- 电子运输链复合体1 (ETC1) 功能因热而受损,选择性地损害TH1细胞.
- 在人类慢性炎症中观察到TH1细胞中DNA损伤和ETC1功能障碍的增加.
结论:
- 发烧相关的温度在TH1细胞中选择性地破坏ETC1,导致细胞亡或适应性变化.
- 暴露于热量可以促进TH1细胞适应,增强效应器功能,同时保持基因组完整性.
- 研究结果表明,发烧在炎症期间调节适应性免疫力方面起着复杂的作用,这对自身免疫和慢性炎症有影响.
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