{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T19:57:59Z","timestamp":1785787079935,"version":"3.56.0"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000833","name":"Rosetrees Trust","doi-asserted-by":"publisher","award":["M678"],"award-info":[{"award-number":["M678"]}],"id":[{"id":"10.13039\/501100000833","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Preschool wheeze attacks triggered by recurrent viral infections, including respiratory syncytial virus (RSV), are associated with an increased risk of childhood asthma. However, mechanisms that lead to asthma following early\u2010life viral wheezing remain uncertain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate a causal relationship between early\u2010life RSV infections and onset of type 2 immunity, we developed a neonatal murine model of recurrent RSV infection, in\u00a0vivo and in silico, and evaluated the dynamical changes of altered airway barrier function and downstream immune responses, including eosinophilia, mucus secretion and type 2 immunity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RSV infection of neonatal BALB\/c mice at 5 and 15\u2009days of age induced robust airway eosinophilia, increased pulmonary CD4<jats:sup>+<\/jats:sup>IL\u201013<jats:sup>+<\/jats:sup> and CD4<jats:sup>+<\/jats:sup>IL\u20105<jats:sup>+<\/jats:sup> cells, elevated levels of IL\u201013 and IL\u20105 and increased airway mucus at 20\u2009days of age. Increased bronchoalveolar lavage albumin levels, suggesting epithelial barrier damage, were present and persisted following the second RSV infection. Computational in silico simulations demonstrated that recurrent RSV infection resulted in severe damage of the airway barrier (epithelium), triggering the onset of type 2 immunity. The in silico results also demonstrated that recurrent infection is not always necessary for the development of type 2 immunity, which could also be triggered with single infection of high viral load or when the epithelial barrier repair is compromised.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The neonatal murine model demonstrated that recurrent RSV infection in early life alters airway barrier function and promotes type 2 immunity. A causal relationship between airway barrier function and type 2 immunity was suggested using in silico model simulations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.14425","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T02:04:10Z","timestamp":1701137050000},"page":"109-119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Role of epithelial barrier function in inducing type 2 immunity following early\u2010life viral infection"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5163-6381","authenticated-orcid":false,"given":"Kunyuan","family":"Tian","sequence":"first","affiliation":[{"name":"National Heart and Lung Institute Imperial College London  London 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