单细胞转录组分析显示,在衰老的败血症期间,骨髓中的免疫重塑
Yijia Lin1,2, Zhiying Zhou1,2, Mingkun Yang3
1Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, No. 1229 Gudun Road, Hangzhou, 310030, Zhejiang, China.
GeroScience
|November 12, 2025
概括
衰老会损害免疫反应,增加败血症的易感性. 这项研究揭示了老年血性干细胞通信受损,为老年人免疫力衰竭提供了潜在的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 老年学是一门学科.
- 血液学 血液学 血液学
背景情况:
- 老龄化增加了由于免疫功能障碍而导致败血症的易感性.
- 老年败血症患者免疫衰竭的机制尚未完全理解.
研究的目的:
- 通过单细胞RNA测序,全面地绘制骨髓免疫细胞在老年败血症中的变化.
- 为了确定关键的细胞间通信通路在老年败血症中被破坏.
- 探索老年人败血症免疫功能障碍的治疗点.
主要方法:
- 在年轻和老年小鼠中,通过结和穿孔 (CLP) 诱导的多微生物败血症.
- 骨髓分析使用单细胞RNA测序和CellChat进行细胞间通信推断.
- 使用Transwell试验评估髓状细胞迁移.
主要成果:
- 老化的败血症小鼠表现出更严重的器官损伤和全身炎症.
- 免疫细胞概况显示适应性免疫力降低,先天免疫力增加.
- 观察到中性粒细胞化学反应受损,高炎症但已耗尽的单细胞/巨细胞,功能障碍的树突细胞,B细胞成熟中断和T细胞程序改变.
- 血液造血干细胞 (HSC) 在老年败血症中扩大,Lgals9-Cd44介导的通信受损,影响髓状细胞迁移.
结论:
- 衰老性败血症的特征是骨髓免疫细胞功能障碍的广泛扩散.
- 通过Lgals9-Cd44轴损坏的HSC-骨髓沟通是老年人败血症免疫力衰竭的关键机制.
- 针对Lgals9-Cd44轴可能会恢复老年人败血症的免疫协调,这需要进一步的临床验证.
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