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

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Yingfeng Zheng1,
Xiuxing Liu1,
Wenqing Le4,
Lihui Xie1,
He Li1,
Wen Wen3,
Si Wang2,6,7,8,
Shuai Ma2,6,7,
Zhaohao Huang1,
Jinguo Ye1,
Wen Shi1,
Yanxia Ye5,
Zunpeng Liu5,7,
Moshi Song2,6,7,
Weiqi Zhang6,7,9,10,
Jing-Dong J. Han11,
Juan Carlos Izpisua Belmonte12,
Chuanle Xiao1,
Jing Qu5,6,7,,,
Hongyang Wang3,,,
Guang-Hui Liu2,6,7,8,,,
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
Funds: This work was supported by the National Key Research and Development Program of China (2017YFA0105804), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16010000), the National Key Research and Development Program of China (2018YFC2000100, 2017YFA0103304, 2017YFA0102802, 2018YFA0107203), the National Natural Science Foundation of China (81670897, 81625009, 91749202, 81861168034, 81921006, 31671429, 91949209, 91749123, 81671377, 81822018, 81870228, 81922027, 81701388, 81601233), the Program of the Beijing Municipal Science and Technology Commission (Z191100001519005), Beijing Natural Science Foundation (Z190019), Beijing Municipal Commission of Health and Family Planning (PXM2018_026283_000002), Advanced Innovation Center for Human Brain Protection (3500-1192012), the Key Research Program of the Chinese Academy of Sciences (KFZDSW-221), K.C. Wong Education Foundation (GJTD-2019-06, GJTD-2019-08), Youth Innovation Promotion Association of CAS (2016093), the State Key Laboratory of Membrane Biology and the State Key Laboratory of Stem Cell and Reproductive Biology.

Received Date: 2020-06-22
Rev Recd Date:2020-07-01
Publish Date:2020-09-27

Abstract

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

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