一个独特的单细胞转录状态将系统性免疫失调与长期COVID中的肺功能障碍联系在一起
Saumya Kumar1,2, Chaofan Li3,4, Liang Zhou1,2
1Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.
Nature immunology
|January 14, 2026
概括
研究人员确定了一种特定的单细胞 (免疫细胞) 状态,与疲劳和呼吸困难等长期COVID症状有关. 这一发现为免疫系统功能障碍和长期COVID疾病的潜在治疗点提供了新的见解.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 病理生理学 病理生理学
背景情况:
- 在长期COVID中免疫失调的机制尚不清楚.
- 长期的COVID与持续的症状和免疫系统的改变有关.
研究的目的:
- 用多omics数据调查长期COVID中的免疫变化.
- 为了确定特定的免疫细胞状态和涉及长期COVID病原发生的途径.
主要方法:
- 集成的单细胞多组数据,免疫分析和功能分析.
- 在多个队伍中分析了循环单细胞和支气管支气管洗样本.
- 与疲劳和呼吸障碍等临床症状相关的免疫细胞状态.
主要成果:
- 确定了一种独特的单细胞转录状态 (LC-Mo),富含轻度至中度急性感染,与持久的CCL2,CXCL11和TNF有关.
- LC-Mo表现出TGFβ和WNT-β-catenin信号,与疲劳严重程度相关.
- 在患有明显疲劳,呼吸不全或严重呼吸道症状的患者中,LC-Mo蛋白标记物升高.
- 表观遗传学分析揭示了LC-Mo.中的AP-1和NF-κB1驱动的益纤维细胞程序.
- 在严重的呼吸病例中,LC-Mo类巨细胞表现出益纤维素特征.
- 高LC-Mo转录状态与干扰素反应受损相关.
结论:
- 定义了一种致病性单细胞转录状态 (LC-Mo),涉及长期COVID.
- 由LC-Mo特征的系统性免疫功能障碍与持续的长期COVID症状有关.
- 提供了机制性见解,并确定了长期COVID疾病的潜在治疗点.
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