{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T21:27:28Z","timestamp":1793914048766,"version":"4.8.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:00:00Z","timestamp":1729209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Severe COVID-19 is associated with neutrophilic inflammation and immunothrombosis. Several members of the IL-17 cytokine family have been associated with neutrophilic inflammation and activation of the endothelium. Therefore, we investigated whether these cytokines were associated with COVID-19.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the association between COVID-19 and circulating plasma levels of IL-17 cytokine family members in participants to the Biobanque qu\u00e9b\u00e9coise de la COVID-19 (BQC19), a prospective observational cohort and an independent cohort from Western University (London, Ontario). We measured the in vitro impact of IL-17F on intercellular adhesion molecule 1 (ICAM-1) cell surface expression and neutrophil adhesion on endothelial cells in culture.  The contribution of two Mitogen Activated Protein Kinase (MAPK) pathways was determined using small molecule inhibitors PD184352 (a MKK1\/MKK2 inhibitor) and BIRB0796 (a p38 MAPK inhibitor).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found increased IL-17D and IL-17F plasma levels when comparing SARS-CoV-2-positive vs negative hospitalized participants. Moreover, increased plasma levels of IL-17D, IL-17E and IL-17F were noted when comparing severe versus mild COVID-19. IL-17F, but not IL-17A, was significantly elevated in people with COVID-19 compared to healthy controls and with more severe disease. In vitro work on endothelial cells treated with IL-17F for 24h showed an increase cell surface expression of ICAM-1 accompanied by neutrophil adhesion. The introduction of two MAPK inhibitors significantly reduced the binding of neutrophils while also reducing ICAM-1 expression at the surface level of endothelial cells, but not its intracellular expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Overall, these results have identified an association between two cytokines of the IL-17 family (IL-17D and IL-17F) with COVID-19 and disease severity. Considering that IL-17F stimulation promotes neutrophil adhesion to the endothelium in a MAPK-dependent manner, it is attractive to speculate that this pathway may contribute to pathogenic immunothrombosis in concert with other molecular effectors.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1452788","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T04:36:59Z","timestamp":1729226219000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Circulating IL-17F, but not IL-17A, is elevated in severe COVID-19 and leads to an ERK1\/2 and p38 MAPK-dependent increase in ICAM-1 cell surface expression and neutrophil adhesion on endothelial 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