A human circulating immune cell landscape in aging and COVID-19

A human circulating immune cell landscape in aging and COVID-19
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衰老和 COVID-19 中的人类循环免疫细胞景观

DOI:
10.1007/s13238-020-00762-2
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发表时间:
2020-08-11
期刊:
影响因子:
21.1
通讯作者:
Su, Wenru
Su, Wenru
中科院分区:
生物学1区
文献类型:
--
作者:
Zheng, Yingfeng;Liu, Xiuxing;Su, Wenru

文献摘要

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与年龄相关的免疫细胞变化与感染风险增加有关。然而,缺乏对人类循环免疫细胞随年龄变化的全面和详细的描述。在这里,我们结合scRNA-seq、细胞计数和scac -seq来比较年轻、老年受试者和COVID-19患者外周血中的免疫细胞类型。我们发现免疫细胞景观随着年龄的增长而重新编程,其特征是T细胞极化,从幼稚细胞和记忆细胞到效应细胞、细胞毒性细胞、耗竭细胞和调节性细胞,以及晚期自然杀伤细胞、年龄相关B细胞、炎症单核细胞和年龄相关树突状细胞增加。此外,与冠状病毒易感性相关的基因的表达随着年龄的增长以细胞亚型特异性的方式上调。值得注意的是,COVID-19促进了年龄诱导的免疫细胞极化和与炎症和细胞衰老相关的基因表达。因此,这些发现表明,与SARS-CoV-2易感性相关的免疫系统失调和基因表达增加可能至少部分解释了老年人易患COVID-19的原因。
Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.