RT info:eu-repo/semantics/article
T1 Altered surface expression of insulin-degrading enzyme on monocytes and lymphocytes from COVID-19 patients both at diagnosis and after hospital discharge
A1 González Casimiro, Carlos Manuel
A1 Arribas Rodríguez, Elisa
A1 Fiz López, Aida
A1 Casas Requena, Javier
A1 Gutiérrez, Sara
A1 Tellería Gómez, Pablo
A1 Novoa, Cristina
A1 Rojo Rello, Silvia
A1 Tamayo Gómez, Eduardo
A1 Orduña Domingo, Antonio
A1 Dueñas Gutiérrez, Carlos Jesús
A1 Bernardo Ordiz, David
A1 Perdomo Hernández, Germán
K1 Insulin-degrading enzyme
K1 COVID-19
K1 Post-COVID-19
K1 Cell Biology
K1 Monocytes
K1 Lymphocytes
K1 Linfocitos
K1 Glucose
K1 Insulin
K1 Insulina
K1 Proteins
K1 Inmunology
K1 2407 Biología Celular
K1 2412 Inmunología
AB Although the COVID-19 disease has developed into a worldwide pandemic, its pathophysiology remains to be fully understood. Insulin-degrading enzyme (IDE), a zinc-metalloprotease with a high affinity for insulin, has been found in the interactomes of multiple SARS-CoV-2 proteins. However, the relevance of IDE in the innate and adaptative immune responses elicited by circulating peripheral blood mononuclear cells is unknown. Here, we show that IDE is highly expressed on the surface of circulating monocytes, T-cells (both CD4+ and CD4−), and, to a lower extent, in B-cells from healthy controls. Notably, IDE’s surface expression was upregulated on monocytes from COVID-19 patients at diagnosis, and it was increased in more severe patients. However, IDE’s surface expression was downregulated (relative to healthy controls) 3 months after hospital discharge in all the studied immune subsets, with this effect being more pronounced in males than in females, and thus it was sex-dependent. Additionally, IDE levels in monocytes, CD4+ T-cells, and CD4− T-cells were inversely correlated with circulating insulin levels in COVID-19 patients (both at diagnosis and after hospital discharge). Of note, high glucose and insulin levels downregulated IDE surface expression by ~30% in the monocytes isolated from healthy donors, without affecting its expression in CD4+ T-cells and CD4− T-cells. In conclusion, our studies reveal the sex- and metabolism-dependent regulation of IDE in monocytes, suggesting that its regulation might be important for the recruitment of immune cells to the site of infection, as well as for glucometabolic control, in COVID-19 patients.
PB MDPI
SN 1422-0067
YR 2022
FD 2022
LK https://uvadoc.uva.es/handle/10324/61385
UL https://uvadoc.uva.es/handle/10324/61385
LA eng
NO International Journal of Molecular Sciences, 2022, Vol. 23, Nº. 19, 11070
NO Producción Científica
DS UVaDOC
RD 23-nov-2024