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    Por favor, use este identificador para citar o enlazar este ítem:https://uvadoc.uva.es/handle/10324/61385

    Título
    Altered surface expression of insulin-degrading enzyme on monocytes and lymphocytes from COVID-19 patients both at diagnosis and after hospital discharge
    Autor
    González Casimiro, Carlos ManuelAutoridad UVA Orcid
    Arribas Rodríguez, ElisaAutoridad UVA Orcid
    Fiz López, AidaAutoridad UVA Orcid
    Casas Requena, JavierAutoridad UVA Orcid
    Gutiérrez, Sara
    Tellería Gómez, PabloAutoridad UVA Orcid
    Novoa, Cristina
    Rojo Rello, SilviaAutoridad UVA Orcid
    Tamayo Gómez, EduardoAutoridad UVA
    Orduña Domingo, AntonioAutoridad UVA
    Dueñas Gutiérrez, Carlos JesúsAutoridad UVA
    Bernardo Ordiz, DavidAutoridad UVA Orcid
    Perdomo Hernández, Germán
    Año del Documento
    2022
    Editorial
    MDPI
    Descripción
    Producción Científica
    Documento Fuente
    International Journal of Molecular Sciences, 2022, Vol. 23, Nº. 19, 11070
    Resumen
    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.
    Materias (normalizadas)
    Insulin-degrading enzyme
    COVID-19
    Post-COVID-19
    Cell Biology
    Monocytes
    Lymphocytes
    Linfocitos
    Glucose
    Insulin
    Insulina
    Proteins
    Inmunology
    Materias Unesco
    2407 Biología Celular
    2412 Inmunología
    ISSN
    1422-0067
    Revisión por pares
    SI
    DOI
    10.3390/ijms231911070
    Patrocinador
    Comisión Europea–NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global) y Junta de Castilla y León - (Proyectos COVID 07.04.467B04.74011.0)
    Fundación “la Caixa” - (grant LCF/PR/PR18/51130007)
    Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación (AEI)/10.13039/501100011033 - (Grant PID2019-110496RB-C22)
    Instituto de Biología y Genética Molecular (IBGM), Junta de Castilla y León - (grant CCVC8485)
    Junta de Castilla y León y Fondo Social Europeo - ((ORDER EDU/574/2018)
    Version del Editor
    https://www.mdpi.com/1422-0067/23/19/11070
    Propietario de los Derechos
    © 2022 The Authors
    Idioma
    eng
    URI
    https://uvadoc.uva.es/handle/10324/61385
    Tipo de versión
    info:eu-repo/semantics/publishedVersion
    Derechos
    openAccess
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    • DEP06 - Artículos de revista [352]
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