{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T15:36:24Z","timestamp":1770910584907,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,6,17]],"date-time":"2015-06-17T00:00:00Z","timestamp":1434499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005640","name":"Flight Attendant Medical Research Institute","doi-asserted-by":"crossref","award":["Clinical Innovator Award"],"award-info":[{"award-number":["Clinical Innovator Award"]}],"id":[{"id":"10.13039\/100005640","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH\/NHLBI","award":["R01-HL07291"],"award-info":[{"award-number":["R01-HL07291"]}]},{"name":"Vermont Lung Center CoBRE","award":["P30-GM103532"],"award-info":[{"award-number":["P30-GM103532"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2015,7]]},"abstract":"Summary<\/jats:title>Background<\/jats:title>Inhalational antigen tolerance typically protects against the development of allergic airway disease but may be overcome to induce allergic sensitization preceding the development of asthma.<\/jats:p><\/jats:sec>Objectives<\/jats:title>We examined in vivo<\/jats:italic> whether pre\u2010existing inhalational antigen tolerance could be overcome by activation of the transcription factor NF<\/jats:styled-content>\u2010\u03baB in conducting airway epithelial cells, and used a combination of in vivo<\/jats:italic> and in vitro<\/jats:italic> approaches to examine the mechanisms involved.<\/jats:p><\/jats:sec>Methods<\/jats:title>Wild\u2010type and transgenic mice capable of expressing constitutively active I\u03baB kinase \u03b2 (CAIKK<\/jats:styled-content>\u03b2) in airway epithelium were tolerized to inhaled ovalbumin. Twenty\u2010eight days later, the transgene was transiently expressed and mice were exposed to inhaled OVA<\/jats:styled-content> on Day 30 in an attempt to overcome inhalational tolerance.<\/jats:p><\/jats:sec>Results<\/jats:title>Following ovalbumin challenge on days 40\u201342, CAIKK<\/jats:styled-content>\u03b2 mice in which the transgene had been activated exhibited characteristic features of allergic airway disease, including airway eosinophilia and methacholine hyper\u2010responsiveness. Increases in the CD<\/jats:styled-content>103+<\/jats:sup> and CD<\/jats:styled-content>11bHI<\/jats:sup><\/jats:styled-content> lung dendritic cell populations were present in CAIKK<\/jats:styled-content>\u03b2 mice on Day 31. Bronchoalveolar lavage from mice expressing CAIKK<\/jats:styled-content>\u03b2 mice induced CD<\/jats:styled-content>4+<\/jats:sup> T cells to secrete TH<\/jats:sub><\/jats:styled-content>2 and TH<\/jats:sub><\/jats:styled-content>17 cytokines, an effect that required IL<\/jats:styled-content>\u20104 and IL<\/jats:styled-content>\u20101 signalling, respectively. CAIKK<\/jats:styled-content>\u03b2 mice on Dox demonstrated increased numbers of innate lymphoid type 2 cells (ILC<\/jats:styled-content>2) in the lung, which also exhibited elevated mRNA<\/jats:styled-content> expression of the TH<\/jats:sub><\/jats:styled-content>2\u2010polarizing cytokine IL<\/jats:styled-content>\u20104. Finally, airway epithelial NF<\/jats:styled-content>\u2010kB<\/jats:styled-content> activation induced allergic sensitization in CAIKK<\/jats:styled-content>\u03b2 mice on Dox that required IL<\/jats:styled-content>\u20104 and IL<\/jats:styled-content>\u20101 signalling in vivo<\/jats:italic>.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Our studies demonstrate that soluble mediators generated in response to airway epithelial NF<\/jats:styled-content>\u2010\u03baB activation orchestrate the breaking of inhalational tolerance and allergic antigen sensitization through the effects of soluble mediators, including IL<\/jats:styled-content>\u20101 and IL<\/jats:styled-content>\u20104, on pulmonary dendritic cells as well as innate lymphoid and CD<\/jats:styled-content>4+<\/jats:sup> T cells.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.12491","type":"journal-article","created":{"date-parts":[[2015,1,23]],"date-time":"2015-01-23T15:27:03Z","timestamp":1422026823000},"page":"1245-1258","source":"Crossref","is-referenced-by-count":21,"title":["Airway epithelial NF<\/scp>\u2010\u03baB activation promotes the ability to overcome inhalational antigen tolerance"],"prefix":"10.1111","volume":"45","author":[{"given":"J. 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