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

Yingfeng Zheng; Xiuxing Liu; Wenqing LE; Lihui Xie; He LI; Wen Wen; Si Wang; Shuai MA; Zhaohao Huang; Jinguo YE; Wen Shi; Yanxia YE; Zunpeng Liu; Moshi Song; Weiqi Zhang; Jing-dong J Han; Juan Carlos Izpisua Belmonte; Chuanle Xiao; Jing QU; Hongyang Wang; Guang-hui Liu; Wenru SU

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

Author: Yingfeng ZHENG ¹ ; Xiuxing LIU ¹ ; Wenqing LE ² ; Lihui XIE ¹ ; He LI ¹ ; Wen WEN ³ ; Si WANG ⁴ ; Shuai MA ⁴ ; Zhaohao HUANG ¹ ; Jinguo YE ¹ ; Wen SHI ¹ ; Yanxia YE ⁵ ; Zunpeng LIU ⁵ ; Moshi SONG ⁴ ; Weiqi ZHANG ⁶ ; Jing-Dong J HAN ⁷ ; Juan Carlos Izpisua BELMONTE ⁸ ; Chuanle XIAO ¹ ; Jing QU ⁹ ; Hongyang WANG ¹⁰ ; Guang-Hui LIU ¹¹ ; Wenru SU ¹²
Author Information

1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
2. Department of Critical Care, Wuhan Hankou Hospital, Wuhan, 430012, China.
3. National Center for Liver Cancer, Second Military Medical University, Shanghai, 200433, China.
4. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, 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. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking University, Beijing, 100871, China.
8. Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
9. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. qujing@ioz.ac.cn.
10. National Center for Liver Cancer, Second Military Medical University, Shanghai, 200433, China. hywangk@vip.sina.com.
11. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. ghliu@ioz.ac.cn.
12. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China. suwenru@gzzoc.com.
Publication Type:Journal Article
Keywords: COVID-19; aging; blood; immune cells; single-cell sequencing
MeSH: Adult; Aged; Aged, 80 and over; Aging; genetics; immunology; Betacoronavirus; CD4-Positive T-Lymphocytes; metabolism; Cell Lineage; Chromatin Assembly and Disassembly; Coronavirus Infections; immunology; Cytokine Release Syndrome; etiology; immunology; Cytokines; biosynthesis; genetics; Disease Susceptibility; Flow Cytometry; methods; Gene Expression Profiling; Gene Expression Regulation, Developmental; Gene Rearrangement; Humans; Immune System; cytology; growth & development; immunology; Immunocompetence; genetics; Inflammation; genetics; immunology; Mass Spectrometry; methods; Middle Aged; Pandemics; Pneumonia, Viral; immunology; Sequence Analysis, RNA; Single-Cell Analysis; Transcriptome; Young Adult
From: Protein & Cell 2020;11(10):740-770
CountryChina
Language:English
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 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.