{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T22:12:44Z","timestamp":1764022364755,"version":"3.45.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19AI125357"],"award-info":[{"award-number":["U19AI125357"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) preferentially infects airway epithelial cells. This infection is mediated by the binding of SARS-CoV-2 spike (S) protein to ACE2 expressed on target cells. Patients with allergic (type-2) asthma have been reported to be less susceptible to coronavirus disease 2019 (COVID-19), but these effects are controversial and mechanistically unclear. We previously showed lower expression of ACE2 mRNA in airway epithelial cells from type-2 asthmatics compared to healthy donors. Moreover, we and others demonstrated that the type-2 cytokine interleukin 13 (IL-13) suppresses ACE2 expression and SARS-CoV-2 infection in human epithelial cells. To better understand the relationship between type-2 inflammation, ACE2 expression, and SARS-CoV-2 infection, we investigated the effects of IL-13 on critical steps of epithelial cell infection by SARS-CoV-2: S protein-mediated binding to ACE2 on epithelial cells, and ACE2-mediated SARS-CoV-2 entry into these cells. Recombinant IL-13 significantly inhibited both these processes. This inhibition appeared to be mediated by IL-13-induced suppression of ACE2 transcription because IL-13 failed to affect S protein-mediated viral entry into cells that express ACE2 under the control of an IL-13 unresponsive heterologous promoter. We propose that IL-13 protects epithelial cells from SARS-CoV-2 infection largely by inhibiting ACE2 expression and ACE2-mediated downstream events that allow the virus to access its cellular targets.<\/jats:p>","DOI":"10.1093\/immhor\/vlaf056","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T22:10:35Z","timestamp":1764022235000},"source":"Crossref","is-referenced-by-count":0,"title":["IL-13 protects epithelial cells from SARS-CoV-2 infection by inhibiting ACE2-mediated virus binding and cell entry"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2276-0321","authenticated-orcid":false,"given":"Vadim","family":"Pivniouk","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Medicine, The University of Arizona , Tucson, AZ 85721,","place":["United States"]},{"name":"Asthma and Airway Disease Research Center, The University of Arizona , Tucson, AZ 85721,","place":["United 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