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.

Bordoni, V., Tartaglia, E., Sacchi, A., Fimia, G. M., Cimini, E., Casetti, R., Notari, S., Grassi, G., Marchioni, L., Bibas, M., Capobianchi, M. R., Locatelli, F., Maeurer, M., Zumla, A., Antinori, A., Nicastri, E., Ippolito, G., Agrati, C., The unbalanced p53/SIRT1 axis may impact lymphocyte homeostasis in COVID-19 patients, <<INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES>>, 2021; 105 (105): 49-53. [doi:10.1016/j.ijid.2021.02.019] [https://hdl.handle.net/10807/228467]

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

Locatelli, Franco
Writing – Review & Editing
;
2021

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.
2021
Inglese
Bordoni, V., Tartaglia, E., Sacchi, A., Fimia, G. M., Cimini, E., Casetti, R., Notari, S., Grassi, G., Marchioni, L., Bibas, M., Capobianchi, M. R., Locatelli, F., Maeurer, M., Zumla, A., Antinori, A., Nicastri, E., Ippolito, G., Agrati, C., The unbalanced p53/SIRT1 axis may impact lymphocyte homeostasis in COVID-19 patients, <<INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES>>, 2021; 105 (105): 49-53. [doi:10.1016/j.ijid.2021.02.019] [https://hdl.handle.net/10807/228467]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/228467
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