系统性炎症会损害人类的骨髓形成和干扰素I型反应
Farid Keramati1,2,3, Guus P Leijte4, Niklas Bruse4
1Department of Molecular Biology, Faculty of Science, Radboud University, Nijmegen, The Netherlands.
Nature immunology
|April 18, 2025
概括
系统性炎症涉及过度炎症,其次是免疫抑制,增加感染风险. 研究人员确定了一种新的单细胞子集和受损的免疫反应,为败血症和COVID-19提供了潜在的治疗点.
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:
- 系统性炎症状况表现出明显的超炎症和免疫抑制阶段.
- 了解驱动这些阶段的机制,特别是免疫抑制和二次感染易感性,仍然不完整.
- 目前的知识差距阻碍了开发有效的治疗策略.
研究的目的:
- 在人类模型中阐明细胞和分子机制,这些机制是系统性炎症的急性和晚期阶段的基础.
- 识别与急性炎症后免疫抑制相关的新型细胞子集和分子特征.
- 探索人类败血症和冠状病毒疾病队伍中发现的翻译相关性.
主要方法:
- 利用受控的人体体内活体模型的脂多糖 (LPS) 诱导的全身炎症.
- 采用单细胞RNA测序 (scRNA-seq) 来分析急性炎症期间的免疫细胞群.
- 在晚期免疫抑制阶段的特征是单细胞反应,骨髓形成和免疫挑战减弱.
- 分析了细菌性败血症和冠状病毒病患者队列,以进行翻译验证.
主要成果:
- 在急性阶段 (4小时LPS后) 确定了一种新的炎症单细胞样子群 (infMono),表达CD163,SLC39A8和CALR.
- 晚期阶段的特征是单细胞I型干扰素 (IFN) 响应基因表达的减少和骨髓形成的受损.
- 在一周后的二次LPS挑战时,观察到免疫反应显著减弱.
- 在人类败血症和COVID-19患者队列中,infMono基因程序和受损骨髓形成被保留.
- 干扰素β (IFNβ) 治疗逆转了I型IFN反应,恢复了细胞因子的产生,并促进了单细胞的成熟.
结论:
- 在系统性炎症的免疫抑制阶段发现了特定的单细胞子集和特征性免疫功能障碍.
- 在细菌性败血症和COVID-19患者中表明存在类似的免疫失调.
- IFNβ作为一种潜在的治疗药物来恢复免疫功能和打击免疫抑制.
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