{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T10:14:49Z","timestamp":1785838489442,"version":"3.56.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:00:00Z","timestamp":1694131200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200035"],"award-info":[{"award-number":["82200035"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170040"],"award-info":[{"award-number":["82170040"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20210957"],"award-info":[{"award-number":["BK20210957"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Neutrophil migration into the airways is a key process in neutrophilic asthma. Developmental endothelial locus\u20101 (DEL\u20101), an extracellular matrix protein, is a neutrophil adhesion inhibitor that attenuates neutrophilic inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Levels of DEL\u20101 were measured in exhaled breath condensate (EBC) and serum in asthma patients by ELISA. DEL\u20101 modulation of neutrophil adhesion and transepithelial migration was examined in a co\u2010culture model in vitro. The effects of DEL\u20101\u2010adenoviral vector\u2010mediated overexpression on ovalbumin\/lipopolysaccharide (OVA\/LPS)\u2010induced neutrophilic asthma were studied in mice in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>DEL\u20101 was primarily expressed in human bronchial epithelial cells and was decreased in asthma patients. Serum DEL\u20101 concentrations were reduced in patients with severe asthma compared with normal subjects (567.1\u2009\u00b1\u200975.3 vs. 276.8\u2009\u00b1\u200929.36\u2009pg\/mL, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001) and were negatively correlated to blood neutrophils (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.2881, <jats:italic>p<\/jats:italic>\u2009=\u2009.0384) and neutrophil\u2010to\u2010lymphocyte ratio (NLR) (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.5469, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001). DEL\u20101 concentrations in the EBC of severe asthmatic patients (113.2\u2009\u00b1\u20098.09\u2009pg\/mL) were also lower than normal subjects (193.0\u2009\u00b1\u20097.61\u2009pg\/mL, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001) and were positively correlated with the asthma control test (ACT) score (<jats:italic>r<\/jats:italic>\u2009=\u20090.3678, <jats:italic>p<\/jats:italic>\u2009=\u2009.0035) and negatively related to EBC IL\u201017 (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.3756, <jats:italic>p<\/jats:italic>\u2009=\u2009.0131), myeloperoxidase (MPO) (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.5967, <jats:italic>p<\/jats:italic>\u2009=\u2009.0055), and neutrophil elastase (NE) (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.5488, <jats:italic>p<\/jats:italic>\u2009=\u2009.0009) expression in asthma patients. Neutrophil adhesion and transepithelial migration in asthma patients were associated with LFA\u20101 binding to ICAM\u20101 and inhibited by DEL\u20101. DEL\u20101 mRNA and protein expression in human bronchial epithelial cells were regulated by IL\u201017. Exogenous DEL\u20101 inhibited IL\u201017\u2010enhanced neutrophil adhesion and migration. DEL\u20101 expression was decreased while neutrophil infiltration was increased in the airway of a murine model of neutrophilic asthma. This was prevented by DEL\u20101 overexpression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>DEL\u20101 down\u2010regulation leads to increased neutrophil migration across bronchial epithelial cells and is associated with neutrophilic airway inflammation in asthma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.15882","type":"journal-article","created":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T08:39:11Z","timestamp":1694162351000},"page":"1180-1194","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["<scp>DEL<\/scp>\u20101, as an anti\u2010neutrophil transepithelial migration molecule, inhibits airway neutrophilic inflammation in asthma"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3682-6432","authenticated-orcid":false,"given":"Man","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Respiratory &amp; Critical Care 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 London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Allergy Pulmonary and Critical Care Medicine Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan China"},{"name":"Shandong Key Laboratory of Infections Respiratory Disease Medical Science and Technology Innovation Center Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujuan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Nanjing Red Cross Hospital  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Nanjing Red Cross Hospital  Nanjing 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