{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:39:58Z","timestamp":1760243998587,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Commission\u2013NextGenerationEU","award":["EU 2020\/2094","LCF\/PR\/PR18\/51130007","PID2019-110496RB-C22","ORDER EDU\/574\/2018"],"award-info":[{"award-number":["EU 2020\/2094","LCF\/PR\/PR18\/51130007","PID2019-110496RB-C22","ORDER EDU\/574\/2018"]}]},{"DOI":"10.13039\/100010434","name":"\u201cLa Caixa\u201d Foundation","doi-asserted-by":"publisher","award":["EU 2020\/2094","LCF\/PR\/PR18\/51130007","PID2019-110496RB-C22","ORDER EDU\/574\/2018"],"award-info":[{"award-number":["EU 2020\/2094","LCF\/PR\/PR18\/51130007","PID2019-110496RB-C22","ORDER EDU\/574\/2018"]}],"id":[{"id":"10.13039\/100010434","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MCIN\/AEI\/10.13039\/501100011033","award":["EU 2020\/2094","LCF\/PR\/PR18\/51130007","PID2019-110496RB-C22","ORDER EDU\/574\/2018"],"award-info":[{"award-number":["EU 2020\/2094","LCF\/PR\/PR18\/51130007","PID2019-110496RB-C22","ORDER EDU\/574\/2018"]}]},{"name":"Programa Estrat\u00e9gico Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), Junta de Castilla y Le\u00f3n","award":["EU 2020\/2094","LCF\/PR\/PR18\/51130007","PID2019-110496RB-C22","ORDER EDU\/574\/2018"],"award-info":[{"award-number":["EU 2020\/2094","LCF\/PR\/PR18\/51130007","PID2019-110496RB-C22","ORDER EDU\/574\/2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2212), and, to a lower extent, in B-cells from healthy controls. Notably, IDE\u2019s surface expression was upregulated on monocytes from COVID-19 patients at diagnosis, and it was increased in more severe patients. However, IDE\u2019s 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\u2212 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\u2212 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.<\/jats:p>","DOI":"10.3390\/ijms231911070","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T01:47:06Z","timestamp":1663811226000},"page":"11070","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered Surface Expression of Insulin-Degrading Enzyme on Monocytes and Lymphocytes from COVID-19 Patients Both at Diagnosis and after Hospital Discharge"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1640-7457","authenticated-orcid":false,"given":"Carlos M.","family":"Gonz\u00e1lez-Casimiro","sequence":"first","affiliation":[{"name":"Physiopathology of Metabolic Diseases Lab, Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), Consejo Superior de Investigaciones Cient\u00edficas (CSIC)-Universidad de Valladolid, 47003 Valladolid (UVa), Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Arribas-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Mucosal Immunology Lab, Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), Consejo Superior de Investigaciones Cient\u00edficas (CSIC)-Universidad de Valladolid (UVa), 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2052-7996","authenticated-orcid":false,"given":"Aida","family":"Fiz-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Mucosal Immunology Lab, Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), Consejo Superior de Investigaciones Cient\u00edficas (CSIC)-Universidad de Valladolid (UVa), 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6413-8127","authenticated-orcid":false,"given":"Javier","family":"Casas","sequence":"additional","affiliation":[{"name":"Microscopy Unit, Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), Consejo Superior de Investigaciones Cient\u00edficas (CSIC)-Universidad de Valladolid (UVa), 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7356-470X","authenticated-orcid":false,"given":"Sara","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Cl\u00ednico Universitario de Valladolid, 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Teller\u00eda","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Cl\u00ednico Universitario de Valladolid, 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Novoa","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Cl\u00ednico Universitario de Valladolid, 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Rojo-Rello","sequence":"additional","affiliation":[{"name":"Microbiology and Immunology Unit, Hospital Cl\u00ednico Universitario de Valladolid, 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Tamayo","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Valladolid, 47002 Valladolid, Spain"},{"name":"Department of Anaesthesiology and Critical Care, Hospital Cl\u00ednico Universitario de Valladolid, 47003 Valladolid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"BioCritic, Group for Biomedical Research in Critical Care Medicine, 47005 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8013-1470","authenticated-orcid":false,"given":"Antonio","family":"Ordu\u00f1a","sequence":"additional","affiliation":[{"name":"Microbiology and Immunology Unit, Hospital Cl\u00ednico Universitario de Valladolid, 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Due\u00f1as","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Cl\u00ednico Universitario de Valladolid, 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Bernardo","sequence":"additional","affiliation":[{"name":"Mucosal Immunology Lab, Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), Consejo Superior de Investigaciones Cient\u00edficas (CSIC)-Universidad de Valladolid (UVa), 47003 Valladolid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2301-0012","authenticated-orcid":false,"given":"German","family":"Perdomo","sequence":"additional","affiliation":[{"name":"Physiopathology of Metabolic Diseases Lab, Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), Consejo Superior de Investigaciones Cient\u00edficas (CSIC)-Universidad de Valladolid, 47003 Valladolid (UVa), Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Casimiro, C.M., Merino, B., Casanueva-\u00c1lvarez, E., 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