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

Shoumit Dey*, Helen Ashwin, Luke Milross, Bethany Hunter, Joaquim Majo, Andrew J Filby, Andrew J Fisher, Paul Kaye, Dimitris Lagos*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)262-275
Number of pages14
JournalClinical and Experimental Immunology
Volume212
Issue number3
Early online date3 Mar 2023
DOIs
Publication statusPublished - 5 Jun 2023

Bibliographical note

© 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

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