IBR1,一种新的内源性IFIH1-结合的dsRNA,控制IFIH1激活和M1巨细胞在ARDS中的极化
Shi Zhang1,2, Wei Huang1, Xueling Wu3
1Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
Clinical and translational medicine
|September 24, 2024
概括
一种新型RNA,即IFIH1结合RNA1 (IBR1),激活单细胞和巨细胞中的IFIH1,导致急性呼吸困扰综合征 (ARDS) 的炎症. 向IBR1或使用IFIH1变体可以治疗ARDS.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 呼吸系统医学 呼吸系统医学
背景情况:
- 来自巨细胞和单细胞的不受控制的炎症加剧了急性呼吸困扰综合征 (ARDS).
- 在肺炎引起的ARDS中,IFIH1对巨细胞两极分化至关重要,但其激活机制尚不清楚.
研究的目的:
- 在ARDS中阐明IFIH1激活的分子机制.
- 研究IFIH1结合RNA1 (IBR1) 在ARDS病变发生过程中的作用.
主要方法:
- 采用了多组学测序和分子相互作用实验.
- 使用了条件基因淘汰赛小鼠和初级细胞.
- 在140名ARDS患者的周围血液细胞中进行定量PCR验证的发现.
主要成果:
- 脂聚糖 (LPS) 通过对内源双链RNA (dsRNA) IBR1的上调激活IFIH1.
- IBR1与IFIH1的螺旋酶域结合,促进M1巨细胞两极分化和ARDS炎症性肺损伤.
- 在患有格拉姆阴性细菌性肺炎的ARDS患者中IBR1表达升高;外体传递的IFIH1突变物抵消了IBR1的影响.
结论:
- 一种新的dsRNA,IBR1,激活IFIH1,在ARDS中驱动巨细胞极化.
- IFIH1变种显示出消除肺部dsRNA和减轻ARDS相关的炎症性肺损伤的潜力.
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