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

TY - JOUR

T1 - Down-regulation of MALAT1 is a hallmark of tissue and peripheral proliferative T cells in COVID-19

AU - Dey, Shoumit

AU - Ashwin, Helen

AU - Milross, Luke

AU - Hunter, Bethany

AU - Majo, Joaquim

AU - Filby, Andrew J

AU - Fisher, Andrew J

AU - Kaye, Paul

AU - Lagos, Dimitris

N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology.

PY - 2023/6/5

Y1 - 2023/6/5

N2 - 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.

AB - 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.

KW - Humans

KW - RNA, Long Noncoding/genetics

KW - Down-Regulation

KW - Cell Proliferation/genetics

KW - COVID-19/genetics

KW - CD8-Positive T-Lymphocytes/metabolism

U2 - 10.1093/cei/uxad034

DO - 10.1093/cei/uxad034

M3 - Article

C2 - 36869729

SN - 0009-9104

VL - 212

SP - 262

EP - 275

JO - Clinical and Experimental Immunology

JF - Clinical and Experimental Immunology

IS - 3

ER -