通过抑制过度的干扰素信号传递,STAT3调节抗病毒免疫力
Shasha Liu1, Siya Liu1, Ziding Yu1
1Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
Cell reports
|July 13, 2023
概括
独立于IL-6的STAT3 Y705酸化对于控制流感等病毒感染至关重要. 这种早期激活的途径可以防止过度产生干扰素,从而限制严重的肺损伤并改善存活率.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 洲际蛋白-6 (IL-6) 是已知的STAT3信号的调节者.
- 病毒感染引发复杂的免疫反应,包括STAT3激活.
- 在病毒感染期间早期STAT3激活的精确机制仍然不完全理解.
研究的目的:
- 调查STAT3 Y705酸化在抗病毒免疫中的作用,独立于IL-6.
- 阐明病毒感染期间参与早期STAT3激活的信号通路.
- 为了确定受损STAT3 Y705酸化对流感A病毒 (IAV) 病原性的影响.
主要方法:
- STAT3 Y705F/+撞击小鼠的一代.
- 小鼠感染流感A病毒 (IAV).
- 对抗病毒基因表达,肺组织损伤,存活率和干扰素生产的分析.
- 在STAT3 Y705F/+小鼠中对IFNAR1和IFNLR1进行基因操纵 (淘汰赛).
主要成果:
- 在病毒感染早期确定了IL-6独立的STAT3 Y705酸化,依赖于RIG-I/MAVS/Syk轴.
- STAT3 Y705F/+小鼠表现出抑制的抗病毒反应,严重的肺损伤和IAV感染后的生存率降低.
- STAT3 Y705酸化通过限制过度的I型和III型干扰素生产来抑制IAV的病原性.
- 阻止STAT3 Y705酸化增加了干扰素表达和IAV病毒性.
- 将IFNAR1或IFNLR1受保护的STAT3 Y705F/+小鼠从肺损伤和减少病毒载量中淘汰.
结论:
- STAT3 Y705酸化对于有效的抗病毒免疫力至关重要.
- 这种酸化通过抑制过度的干扰素信号作用,从而防止有害的炎症和组织损伤.
- 准这种途径可能为管理病毒感染提供新的策略.
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