通过I型和II型干扰子激活cGAS-STING-IRF3轴,有助于主机防御
Zhen Tong1,2, Jia-Peng Zou1,2, Su-Yun Wang1
1Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|July 15, 2024
概括
干扰子 (IFN) 与STAT1一起激活IRF3通路,揭示了对病原体和瘤的宿主防御的新机制. 这条涉及cGAS-STING-TBK1的途径对于抗病毒和抗瘤活动至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
背景情况:
- 干扰子 (IFN) 对宿主防御至关重要,主要是激活JAK-STAT通路以诱导效应基因.
- 众所周知,转录因子IRF3在天生的免疫力中起作用,但其与IFN的确切参与程度不太清楚.
研究的目的:
- 阐明一种新的干扰素 (IFN) 信号传递途径,涉及转录因子IRF3.
- 研究IFN,线粒体DNA释放和宿主防御中的cGAS-STING-TBK1轴之间的机制联系.
主要方法:
- 研究了IRF3和STAT1通过I型 (IFN-β) 和II型 (IFN-γ) 干扰素的激活.
- 利用基因缺陷模型 (IRF3,cGAS,STING) 来评估功能后果.
- 使用生物化学分析检查了线粒体DNA释放和cGAS酸化.
主要成果:
- 证明IFN-β和IFN-γ都与STAT1.1并行激活IRF3,并与STAT1.3并行激活IRF3.
- 缺少IRF3会影响特定的IFN诱导的效应基因的转录.
- 由IFN诱导的IRF3激活取决于cGAS-STING-TBK1轴,涉及线粒体DNA释放和JAK1-介导的cGAS酸化.
- 缺少cGAS,STING或IRF3,影响了由IFN调解的抗病毒和抗瘤反应.
结论:
- 确定了一种新的IRF3激活途径,与IFN触发的正规JAK-STAT途径并行.
- cGAS-STING-IRF3轴在IFN介导的抗病毒和抗瘤免疫中发挥着重要作用.
- 这一发现为cGAS-STING-IRF3途径在宿主防御中的多样性作用提供了机制性的解释.
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