一种I型的干扰素-线粒体轴调节了巨细胞的雌激细胞和干扰素刺激的基因诱导
Gillian Dunphy1, Irene Adán-Barrientos2, Irene Fernández-Delgado3
1Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain.
Immunity
|January 29, 2026
概括
细胞核酸传感,通过干扰素α/β受体 (IFNAR) 信号传导,通过改变线粒体功能和限制炎症来增强巨细胞效细胞化. 这种途径可以促进细胞增生,同时控制干扰素刺激的基因诱导,以解决炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞的新陈代谢
- 分子生物学分子生物学
背景情况:
- 巨细胞的代谢重编程对于免疫细胞功能至关重要.
- 细胞核酸感应对巨细胞代谢的影响不同于托尔类受体刺激.
研究的目的:
- 研究细胞核酸在巨细胞中感应的代谢和功能后果.
- 阐明干扰素α/β受体 (IFNAR) 信号传导在这个过程中的作用.
主要方法:
- 分析线粒体膜潜力 (MMP) 和呼吸.
- 评估干扰素刺激的15 (ISG15) 基因表达和蛋白质ISGylation.
- 研究线粒体蛋白酶OMA1活动和线粒体动态.
- 评估细胞内膜网膜 - 线粒体通信和基因素乙化.
- 评估巨细胞的细胞能力和对病毒感染的保护.
主要成果:
- 细胞核酸感应降低了MMP,但维持了线粒体呼吸,这取决于IFNAR信号.
- IFNAR信号诱导了线粒体蛋白质的ISG15表达和ISGylation,增加了ATP的产生,并增强了细胞分裂.
- IFNAR-ISG15通路激活了OMA1,导致线粒体裂变并减少了ER-线粒体通信,从而抑制了ISG诱导.
- 损失ISG15或OMA1导致增强ISG诱导和基因素乙化,这取决于线粒体的摄取量,从而提供对病毒感染的保护.
结论:
- 通过调节线粒体功能,IFNAR-ISG15信号增强了巨细胞的效细胞化.
- 这一途径限制了过度的ISG诱导,促进了炎症的解决.
- 这些发现揭示了通过巨细胞代谢平衡免疫激活和解消的机制.
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