The unbalanced p53/SIRT1 axis may impact lymphocyte homeostasis in COVID-19 patients.
Int J Infect Dis
; 105: 49-53, 2021 Apr.
Article
in En
| MEDLINE
| ID: mdl-33578018
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 (IL1ß, 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-1ß r = 0.5 and p = 0.05; IL-8 r = 0.5 and p = 0.05) and negatively with SIRT1 (IL1-ß 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lymphocytes
/
Tumor Suppressor Protein p53
/
Sirtuin 1
/
SARS-CoV-2
/
COVID-19
/
Homeostasis
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Int J Infect Dis
Journal subject:
DOENCAS TRANSMISSIVEIS
Year:
2021
Document type:
Article
Affiliation country:
Italy