辐射诱导的ecirp会通过线粒体损伤和铁致死引起巨的细胞功能障碍
Mian Zhou1, Gaifeng Ma1, Jingsong Li1
1Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY, United States.
Frontiers in immunology
|December 8, 2025
概括
辐射暴露会触发细胞外冷诱导性RNA结合蛋白 (eCIRP) 的释放,通过铁亡和线粒体损伤引起巨细胞功能障碍. 用MOP3抑制eCIRP可以恢复免疫功能,为辐射损伤提供潜在的治疗方法.
科学领域:
- 免疫学 免疫学 免疫学
- 辐射生物学 辐射生物学
- 细胞生物学 细胞生物学
背景情况:
- 电离辐射会损害免疫功能,增加感染风险和死亡率.
- 辐射后,细胞外冷诱导性RNA结合蛋白 (eCIRP) 被释放出来.
- 辐射诱导的免疫功能障碍涉及巨细胞的细胞功能障碍.
研究的目的:
- 调查辐射诱导的eCIRP释放导致巨细胞细胞功能障碍的机制.
- 确定铁和线粒体功能障碍在这个过程中的作用.
- 为了评估eCIRP抑制剂的治疗潜力.
主要方法:
- 腹膜巨细胞被暴露在10-Gy辐射中.
- 评估了eCIRP水平,铁亡标志物 (脂质过氧化,GPX4),线粒体功能 (海马试验) 和细胞活性 (大肠杆菌吸收).
- 评估了eCIRP抑制剂MOP3的影响.
主要成果:
- 辐射诱导了巨细胞中的铁和线粒体功能障碍.
- eCIRP释放与增加的铁和食细胞功能障碍相关.
- MOP3治疗恢复了线粒体功能,降低了铁亡,改善了细胞化.
结论:
- 辐射诱导的ecirp释放通过线粒体损伤和铁亡驱动巨细胞功能障碍.
- 用MOP3等抑制剂向eCIRP是一种有前途的治疗策略,可以缓解辐射引起的免疫缺陷.
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