在先天免疫细胞及其原始体中对冠状病毒感染的表观遗传记忆
Jin-Gyu Cheong1, Arjun Ravishankar2, Siddhartha Sharma3
1Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Medicine, New York, NY 10065, USA.
Cell
|August 19, 2023
概括
严重的COVID-19可以重新编程造血干细胞和原始细胞 (HSPC),从而创造持久的先天免疫记忆. 这些HSPC及其后代的表观遗传变化可能解释了幸存者的长期免疫功能障碍.
科学领域:
- 免疫学
- 干细胞生物学
- 传染性疾病
背景情况:
- 炎症可能导致持续的细胞变化.
- 人类感染对造血干细胞和原始细胞 (HSPC) 的先天免疫记忆的影响尚不清楚.
研究的目的:
- 调查感染和炎症是否以及如何在人类HSPC中建立先天免疫记忆.
- 在2019年严重的冠状病毒病 (COVID-19) 之后,探索HSPC的长期表观基因重编程.
主要方法:
- 从COVID-19患者的外周血液中分析循环的HSPC.
- 表观基因分析以确定HSPC的变化.
- 研究转录因子 (TF) 活动和炎症基因调节.
- 使用鼠标模型进行冠状病毒感染.
主要成果:
- 在严重的COVID-19后,HSPC的表观遗传重编程和改变的先天免疫表型持续数月至一年.
- 这些变化与特定的TF活动,炎症调节和骨髓形成的增加有关.
- 在HSPC的表观遗传变化被传递给分化的后代免疫细胞.
- 早期的IL-6活性在持续的表型中起到了作用.
结论:
- 感染后HSPC的表观遗传重编可以导致持久的先天免疫记忆.
- 这种重新编程可能是COVID-19等感染后免疫功能变化的基础.
- 这些发现对于了解和治疗数百万 COVID-19 幸存者的长期免疫后果具有重要意义.
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