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Downregulation of MALAT1 is a hallmark of tissue and peripheral proliferative T cells in COVID-19

Lookup NU author(s): Dr Luke Milross, Bethany Hunter, Dr Joaquim Majo, Professor Andrew FilbyORCiD, Professor Andrew FisherORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2023 The Author(s). Published by Oxford University Press on behalf of the British Society for Immunology.T cells play key protective but also pathogenic roles in COVID-19. We studied the 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 the 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.

Publication metadata

Author(s): Dey S, Ashwin H, Milross L, Hunter B, Majo J, Filby AJ, Fisher AJ, Kaye PM, Lagos D

Publication type: Article

Publication status: Published

Journal: Clinical and Experimental Immunology

Year: 2023

Volume: 212

Issue: 3

Pages: 262-275

Print publication date: 01/06/2023

Online publication date: 03/03/2023

Acceptance date: 01/03/2023

Date deposited: 10/07/2023

ISSN (print): 0009-9104

ISSN (electronic): 1365-2249

Publisher: Oxford University Press

URL: https://doi.org/10.1093/cei/uxad034

DOI: 10.1093/cei/uxad034

PubMed id: 36869729

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