UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

The unbalanced p53/SIRT1 axis may impact lymphocyte homeostasis in COVID-19 patients

Bordoni, V; Tartaglia, E; Sacchi, A; Fimia, GM; Cimini, E; Casetti, R; Notari, S; ... Agrati, C; + view all (2021) The unbalanced p53/SIRT1 axis may impact lymphocyte homeostasis in COVID-19 patients. International Journal of Infectious Diseases , 105 pp. 49-53. 10.1016/j.ijid.2021.02.019. Green open access

[thumbnail of Zumla_The unbalanced p53:SIRT1 axis may impact lymphocyte homeostasis in COVID-19 patients_VoR.pdf]
Preview
Text
Zumla_The unbalanced p53:SIRT1 axis may impact lymphocyte homeostasis in COVID-19 patients_VoR.pdf - Published Version

Download (1MB) | Preview

Abstract

BACKGROUND/OBJECTIVES: A dysregulated inflammatory profile plays an important role in coronavirus disease-2019 (COVID-19) pathogenesis. Moreover, the depletion of lymphocytes is typically associated with an unfavourable disease course. We studied the role and impact of p53 and deacetylase Sirtuin 1 (SIRT1) on lymph-monocyte homeostasis and their possible effect on T and B cell signalling. METHODS: Gene expression analysis and flow cytometry were performed on peripheral blood mononuclear cells (PBMC) of 35 COVID-19 patients and 10 healthy donors (HD). Inflammatory cytokines, the frequency of Annexin+ cells among CD3+ T cells and CD19+ B cell subsets were quantified. RESULTS: PBMC from COVID-19 patients had a higher p53 expression, and higher concentrations of plasma proinflammatory cytokines (IL1β, TNF-α, IL8, and IL6) than HD. Deacetylase Sirtuin 1 (SIRT1) expression was significantly decreased in COVID-19 patients and was negatively correlated with p53 (p = 0.003 and r = -0.48). A lower expression of IL-7R and B Cell linker (BLNK), key genes for lymphocyte homeostasis and function, was observed in COVID-19 than in HD. The reduction of IgK and IgL chains was seen in lymphopenic COVID-19 patients. A significant increase in both apoptotic B and T cells were observed. Inflammatory cytokines correlated positively with p53 (IL-1β: r = 0.5 and p = 0.05; IL-8: r = 0.5 and p = 0.05) and negatively with SIRT1 (IL1-β: r = -0.5 and p = 0.04; TNF-α: r = -0.4 and p = 0.04). CONCLUSIONS: Collectively, our data indicate that the inflammatory environment, the dysregulated p53/SIRT1 axis and low expression of IL7R and BLNK may impact cell survival, B cell signalling and antibody production in COVID-19 patients. Further studies are required to define the functional impact of low BLNK/IL7R expression during severe acute respiratory syndrome coronavirus-2 infection.

Type: Article
Title: The unbalanced p53/SIRT1 axis may impact lymphocyte homeostasis in COVID-19 patients
Location: Canada
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ijid.2021.02.019
Publisher version: https://doi.org/10.1016/j.ijid.2021.02.019
Language: English
Additional information: Copyright © 2021 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: BLNK, COVID-19, IL-7R, Inflammation, p53/SIRT1
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10124183
Downloads since deposit
64Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item