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

Int J Infect Dis. 2021 Apr:105:49-53. doi: 10.1016/j.ijid.2021.02.019. Epub 2021 Feb 10.

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.

Keywords: BLNK; COVID-19; IL-7R; Inflammation; p53/SIRT1.

MeSH terms

  • Aged
  • COVID-19 / immunology*
  • Cytokines / blood
  • Female
  • Homeostasis*
  • Humans
  • Lymphocytes / immunology*
  • Male
  • Middle Aged
  • SARS-CoV-2*
  • Sirtuin 1 / physiology*
  • Tumor Suppressor Protein p53 / physiology*

Substances

  • Cytokines
  • Tumor Suppressor Protein p53
  • SIRT1 protein, human
  • Sirtuin 1