效应记忆T细胞通过触发DNA损伤和树突细胞中非正规的STING通路来诱导先天性炎症
Hannah E Meibers1, Kathrynne A Warrick1, Andrew VonHandorf2
1Immunology Graduate Program, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Cell reports
|October 5, 2023
概括
CD4+效应体记忆T细胞诱导树突细胞中的DNA损伤,激活一种新的STING-NF-κB通路. 这种由T细胞驱动的炎症为自身免疫性疾病和细胞因子风暴提供了一个新的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- CD4+效应体内存T (TEM) 细胞和树突细胞 (DCs) 之间的协同相互作用驱动先天性炎症性细胞因子的产生,导致自身免疫病理和细胞因子风暴.
- 虽然TEM细胞通过TNF超级家族连体激活DC,但它们在诱导DC内在变化影响先天性炎症方面的作用仍未被探索.
研究的目的:
- 研究TEM细胞是否诱导DC内在变化,调节先天性炎症反应.
- 阐明TEM细胞在DC中引发炎症的分子机制.
主要方法:
- 研究了TEM细胞和DC相互作用.
- 在DC中评估了线粒体的活性氧物种 (ROS) 生产和DNA双链断裂.
- 分析了循环瓜诺辛单酸盐 (GMP) -AMP合成酶 (cGAS) -独立于STING-TRAF6-NF-κB信号轴的激活.
- 利用STING缺陷的DC来评估该途径在细胞因子生产中的作用.
主要成果:
- 通过线粒体ROS生产,TEM细胞诱导DC中的双链DNA断裂.
- 在TEM细胞相互作用时,在DC中观察到cGAS独立的,非正规的STING-TRAF6-NF-κB信号轴的激活.
- 在TEM细胞相互作用后,STING缺乏的DCs表现出NF-κB激活的减少和IL-1β和IL-6的产生受损.
结论:
- TEM细胞通过DNA损伤和非正规的STING-NF-κB通路触发DCs中的先天性炎症.
- 这种新发现的途径代表了一种潜在的治疗点,用于缓解自身免疫性疾病和细胞因子风暴中的T细胞驱动炎症.
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