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

doi:10.1007/s13238-020-00762-2

Protein Cell

2020, Vol. 11

Issue (10) : 740-770 https://doi.org/10.1007/s13238-020-00762-2

RESEARCH ARTICLE

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

Yingfeng Zheng¹, Xiuxing Liu¹, Wenqing Le⁴, Lihui Xie¹, He Li¹, Wen Wen³, Si Wang^2,^6,^7,⁸, Shuai Ma^2,^6,⁷, Zhaohao Huang¹, Jinguo Ye¹, Wen Shi¹, Yanxia Ye⁵, Zunpeng Liu^5,⁷, Moshi Song^2,^6,⁷, Weiqi Zhang^6,^7,^9,¹⁰, Jing-Dong J. Han¹¹, Juan Carlos Izpisua Belmonte¹², Chuanle Xiao¹, Jing Qu^5,^6,⁷(

), Hongyang Wang³(

), Guang-Hui Liu^2,^6,^7,⁸(

), Wenru Su¹(

)

¹. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China
². State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
³. National Center for Liver Cancer, Second Military Medical University, Shanghai 200433, China
⁴. Department of Critical Care, Wuhan Hankou Hospital, Wuhan 430012, China
⁵. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
⁶. Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China
⁷. University of Chinese Academy of Sciences, Beijing 100049, China
⁸. Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China
⁹. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
¹⁰. China National Center for Bioinformation, Beijing 100101, China
¹¹. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking University, Beijing 100871, China
¹². Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA

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Abstract

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 subtypespecific 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.

Keywords aging single-cell sequencing blood COVID-19 immune cells

Corresponding Author(s): Jing Qu,Hongyang Wang,Guang-Hui Liu,Wenru Su

Online First Date: 22 September 2020 Issue Date: 12 October 2020

Cite this article:

Yingfeng Zheng,Xiuxing Liu,Wenqing Le, et al. A human circulating immune cell landscape in aging and COVID-19[J]. Protein Cell, 2020, 11(10): 740-770.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-020-00762-2
https://academic.hep.com.cn/pac/EN/Y2020/V11/I10/740

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