Dey, Shoumit orcid.org/0000-0003-2655-9921, Ashwin, Helen, Milross, Luke et al. (6 more authors) (2023) Down-regulation of MALAT1 is a hallmark of tissue and peripheral proliferative T cells in COVID-19. Clinical and Experimental Immunology. pp. 262-275. ISSN 0009-9104
Abstract
T cells play key protective but also pathogenic roles in COVID-19. We studied expression of long non-coding RNAs (lncRNAs) in COVID-19 T cell transcriptomes by integrating previously published single-cell RNA sequencing datasets. The long intergenic non-coding RNA MALAT1 was the most highly transcribed lncRNA in T cells, with Th1 cells demonstrating the lowest and CD8+ resident memory cells the highest MALAT1 expression, amongst CD4+ and CD8+ T cells populations, respectively. We then identified gene signatures that covaried with MALAT1 in single T cells. A significantly higher number of transcripts correlated negatively with MALAT1 than those that correlated. Enriched functional annotations of the MALAT1- anti-correlating gene signature included processes associated with T cell activation such as cell division, oxidative phosphorylation and response to cytokine. The MALAT1 anti-correlating gene signature shared by both CD4+ and CD8+ T cells marked dividing T cells in both lung and blood of COVID-19 patients. Focussing on the tissue, we used an independent patient cohort of post-mortem COVID-19 lung samples and demonstrated that MALAT1 suppression was indeed a marker of MKI67+ proliferating CD8+ T cells. Our results reveal MALAT1 suppression and its associated gene signature are a hallmark of human proliferating T cells.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. |
Keywords: | Humans,RNA, Long Noncoding/genetics,Down-Regulation,Cell Proliferation/genetics,COVID-19/genetics,CD8-Positive T-Lymphocytes/metabolism |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Hull York Medical School (York) |
Depositing User: | Pure (York) |
Date Deposited: | 03 Dec 2024 17:20 |
Last Modified: | 21 Jan 2025 18:08 |
Published Version: | https://doi.org/10.1093/cei/uxad034 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1093/cei/uxad034 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:220418 |
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Description: Downregulation of MALAT1 is a hallmark of tissue and peripheral proliferative T cells in COVID-19
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