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Single-cell transcriptomics reveal a unique memory-like NK cell subset that accumulates with ageing and correlates with disease severity in COVID-19

BACKGROUND: Natural killer (NK) cells are innate lymphoid cells that mediate antitumour and antiviral responses. However, very little is known about how ageing influences human NK cells, especially at the single-cell level. METHODS: We applied single-cell sequencing (scRNA-seq) to human lymphocytes...

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Autores principales: Guo, Chuang, Wu, Mingming, Huang, Beibei, Zhao, Rui, Jin, Linlin, Fu, Binqing, Wang, Ping, Wang, Dongyao, Zheng, Meijuan, Fang, Jingwen, Wei, Haiming, Qu, Kun, Ni, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9060844/
https://www.ncbi.nlm.nih.gov/pubmed/35501841
http://dx.doi.org/10.1186/s13073-022-01049-3
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author Guo, Chuang
Wu, Mingming
Huang, Beibei
Zhao, Rui
Jin, Linlin
Fu, Binqing
Wang, Ping
Wang, Dongyao
Zheng, Meijuan
Fang, Jingwen
Wei, Haiming
Qu, Kun
Ni, Fang
author_facet Guo, Chuang
Wu, Mingming
Huang, Beibei
Zhao, Rui
Jin, Linlin
Fu, Binqing
Wang, Ping
Wang, Dongyao
Zheng, Meijuan
Fang, Jingwen
Wei, Haiming
Qu, Kun
Ni, Fang
author_sort Guo, Chuang
collection PubMed
description BACKGROUND: Natural killer (NK) cells are innate lymphoid cells that mediate antitumour and antiviral responses. However, very little is known about how ageing influences human NK cells, especially at the single-cell level. METHODS: We applied single-cell sequencing (scRNA-seq) to human lymphocytes and NK cells from 4 young and 4 elderly individuals and then analysed the transcriptome data using Seurat. We detected the proportion and phenotype of NK cell subsets in peripheral blood samples from a total of 62 young and 52 elderly healthy donors by flow cytometry. We also used flow cytometry to examine the effector functions of NK cell subsets upon IFN-α/IL-12+IL-15/K562/IL-2 stimulation in vitro in peripheral blood samples from a total of 64 young and 63 elderly healthy donors. We finally studied and integrated single-cell transcriptomes of NK cells from 15 young and 41 elderly COVID-19 patients with those from 12 young and 6 elderly healthy control individuals to investigate the impacts of ageing on NK cell subsets in COVID-19 disease. RESULTS: We discovered a memory-like NK subpopulation (NK2) exhibiting the largest distribution change between elderly and young individuals among lymphocytes. Notably, we discovered a unique NK subset that was predominantly CD52(+) NK2 cells (NK2.1). These memory-like NK2.1 cells accumulated with age, exhibited proinflammatory characteristics, and displayed a type I interferon response state. Integrative analyses of a large-cohort COVID-19 dataset and our datasets revealed that NK2.1 cells from elderly COVID-19 patients are enriched for type I interferon signalling, which is positively correlated with disease severity in COVID-19. CONCLUSIONS: We identified a unique memory-like NK cell subset that accumulates with ageing and correlates with disease severity in COVID-19. Our results identify memory-like NK2.1 cells as a potential target for developing immunotherapies for infectious diseases and for addressing age-related dysfunctions of the immune system. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13073-022-01049-3.
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spelling pubmed-90608442022-05-03 Single-cell transcriptomics reveal a unique memory-like NK cell subset that accumulates with ageing and correlates with disease severity in COVID-19 Guo, Chuang Wu, Mingming Huang, Beibei Zhao, Rui Jin, Linlin Fu, Binqing Wang, Ping Wang, Dongyao Zheng, Meijuan Fang, Jingwen Wei, Haiming Qu, Kun Ni, Fang Genome Med Research BACKGROUND: Natural killer (NK) cells are innate lymphoid cells that mediate antitumour and antiviral responses. However, very little is known about how ageing influences human NK cells, especially at the single-cell level. METHODS: We applied single-cell sequencing (scRNA-seq) to human lymphocytes and NK cells from 4 young and 4 elderly individuals and then analysed the transcriptome data using Seurat. We detected the proportion and phenotype of NK cell subsets in peripheral blood samples from a total of 62 young and 52 elderly healthy donors by flow cytometry. We also used flow cytometry to examine the effector functions of NK cell subsets upon IFN-α/IL-12+IL-15/K562/IL-2 stimulation in vitro in peripheral blood samples from a total of 64 young and 63 elderly healthy donors. We finally studied and integrated single-cell transcriptomes of NK cells from 15 young and 41 elderly COVID-19 patients with those from 12 young and 6 elderly healthy control individuals to investigate the impacts of ageing on NK cell subsets in COVID-19 disease. RESULTS: We discovered a memory-like NK subpopulation (NK2) exhibiting the largest distribution change between elderly and young individuals among lymphocytes. Notably, we discovered a unique NK subset that was predominantly CD52(+) NK2 cells (NK2.1). These memory-like NK2.1 cells accumulated with age, exhibited proinflammatory characteristics, and displayed a type I interferon response state. Integrative analyses of a large-cohort COVID-19 dataset and our datasets revealed that NK2.1 cells from elderly COVID-19 patients are enriched for type I interferon signalling, which is positively correlated with disease severity in COVID-19. CONCLUSIONS: We identified a unique memory-like NK cell subset that accumulates with ageing and correlates with disease severity in COVID-19. Our results identify memory-like NK2.1 cells as a potential target for developing immunotherapies for infectious diseases and for addressing age-related dysfunctions of the immune system. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13073-022-01049-3. BioMed Central 2022-05-03 /pmc/articles/PMC9060844/ /pubmed/35501841 http://dx.doi.org/10.1186/s13073-022-01049-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Guo, Chuang
Wu, Mingming
Huang, Beibei
Zhao, Rui
Jin, Linlin
Fu, Binqing
Wang, Ping
Wang, Dongyao
Zheng, Meijuan
Fang, Jingwen
Wei, Haiming
Qu, Kun
Ni, Fang
Single-cell transcriptomics reveal a unique memory-like NK cell subset that accumulates with ageing and correlates with disease severity in COVID-19
title Single-cell transcriptomics reveal a unique memory-like NK cell subset that accumulates with ageing and correlates with disease severity in COVID-19
title_full Single-cell transcriptomics reveal a unique memory-like NK cell subset that accumulates with ageing and correlates with disease severity in COVID-19
title_fullStr Single-cell transcriptomics reveal a unique memory-like NK cell subset that accumulates with ageing and correlates with disease severity in COVID-19
title_full_unstemmed Single-cell transcriptomics reveal a unique memory-like NK cell subset that accumulates with ageing and correlates with disease severity in COVID-19
title_short Single-cell transcriptomics reveal a unique memory-like NK cell subset that accumulates with ageing and correlates with disease severity in COVID-19
title_sort single-cell transcriptomics reveal a unique memory-like nk cell subset that accumulates with ageing and correlates with disease severity in covid-19
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9060844/
https://www.ncbi.nlm.nih.gov/pubmed/35501841
http://dx.doi.org/10.1186/s13073-022-01049-3
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