Z-核酸感应触发了ZBP1依赖性亡和炎症
Huipeng Jiao1,2, Laurens Wachsmuth1,2, Snehlata Kumari1,2
1Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Nature
|April 17, 2020
概括
Z-DNA结合蛋白1 (ZBP1) 能够感知内源Z型核酸,从而引发亡和炎症. 这一发现揭示了ZBP1
科学领域:
- 分子生物学
- 免疫学
- 遗传学
背景情况:
- Z-DNA和Z-RNA的生物学作用在很大程度上是未知的.
- Z-DNA结合蛋白1 (ZBP1) 是Z型核酸的传感器,参与宿主对病毒的防御.
- 在没有病毒感染的情况下ZBP1的激活尚不清楚.
研究的目的:
- 研究由内源性配体激活ZBP1的机制.
- 阐明ZBP1在非病毒性炎症中的作用.
主要方法:
- 使用具有特定基因突变的小鼠模型 (Ripk1mR/mR,RIPK1E-KO,FADDIEC-KO).
- 在各种组织中评估ZBP1介导的亡和炎症.
- 研究ZBP1与细胞核酸的结合以及Zα域的作用.
主要成果:
- 对内源配体的Zα依赖感应诱导ZBP1介导的围产死亡,皮肤炎症和结肠炎.
- 功能Zα域对于ZBP1诱导的亡是必不可少的.
- ZBP1激活可以发生在核中,这表明核Z型核酸的识别,可能来自内源的反元素.
结论:
- 通过ZBP1感知内源Z型核酸会触发RIPK3依赖性亡和炎症.
- 这种途径可能导致慢性炎症,特别是在具有RIPK1和CASP8突变的个体中.
- 鉴定了来自反元素的内源双链RNA作为潜在的ZBP1连接体.
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