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Genome wide association studies have described associations between ST2\/Interleukin (IL)\u201033 genes in asthma, but its role in bronchial epithelium is unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>ST2 expression was examined in subjects with asthma and healthy controls in bronchial epithelium from biopsies (n\u00a0=\u00a027 versus n\u00a0=\u00a09) and brushings (n\u00a0=\u00a034 versus n\u00a0=\u00a020) by immunohistochemistry and RNA\u2010Seq. In human primary bronchial epithelial cells ST2 mRNA and protein expression were assessed by qPCR, flow cytometry, Western blotting, and immunofluorescence. IL\u201033 function in epithelial cells was examined by intracellular calcium measurements, wound healing assays, and synthetic activation by gene array and ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Bronchial epithelial ST2 protein expression was significantly decreased in biopsies in subjects with asthma compared to healthy controls (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.039). <jats:italic>IL1RL1<\/jats:italic> gene expression in bronchial brushes was not different between health and disease. In vitro primary bronchial epithelial cells expressed ST2 and IL\u201033 stimulation led to an increase in intracellular calcium, altered gene expression, but had no effect upon wound repair. Epithelial cells released sST2 spontaneously, which was reduced following stimulation with TNF\u03b1 or poly\u2010IC. Stimulation by TNF\u03b1 or poly\u2010IC did not affect the total ST2 expression by epithelial cell whereas surface ST2 decreased in response to TNF\u03b1, but not poly\u2010IC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In asthma, bronchial epithelium protein expression of ST2 is decreased. Our in vitro findings suggest that this decrease might be a consequence of the pro\u2010inflammatory environment in asthma or in response to viral infection.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.14436","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T18:16:10Z","timestamp":1591726570000},"page":"3184-3194","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["ST2 expression and release by the bronchial epithelium is downregulated in asthma"],"prefix":"10.1111","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8875-0660","authenticated-orcid":false,"given":"Davinder","family":"Kaur","sequence":"first","affiliation":[{"name":"Institute for Lung Health Department of Respiratory Sciences University of Leicester Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Latifa","family":"Chachi","sequence":"additional","affiliation":[{"name":"Institute for Lung Health Department of Respiratory Sciences University of Leicester Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Gomez","sequence":"additional","affiliation":[{"name":"Institute for Lung Health Department of Respiratory Sciences University of Leicester Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Sylvius","sequence":"additional","affiliation":[{"name":"Genomic Core Facility Department of Genetics University of Leicester Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shailendra R.","family":"Singh","sequence":"additional","affiliation":[{"name":"Institute for Lung Health Department of Respiratory Sciences University of Leicester Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammadali Y.","family":"Ramsheh","sequence":"additional","affiliation":[{"name":"Institute for Lung Health Department of Respiratory Sciences University of Leicester Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8893-6687","authenticated-orcid":false,"given":"Ruth","family":"Saunders","sequence":"additional","affiliation":[{"name":"Institute for Lung Health Department of Respiratory Sciences University of Leicester Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Brightling","sequence":"additional","affiliation":[{"name":"Institute for Lung Health Department of Respiratory Sciences University of Leicester Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2004.00526.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.07.019"},{"issue":"18","key":"e_1_2_8_4_1","first-page":"30389","article-title":"Moderate\u2010to\u2010severe asthma in individuals of European ancestry: a genome\u2010wide association study","volume":"2213","author":"Shrine N","year":"2018","journal-title":"Lancet Respir Med."},{"issue":"7","key":"e_1_2_8_5_1","first-page":"499","article-title":"Effect of tralokinumab, an interleukin\u201013 neutralising monoclonal antibody, on eosinophilic airway inflammation in uncontrolled moderate\u2010to\u2010severe asthma (MESOS): a multicentre, double\u2010blind, randomised, placebo\u2010controlled phase 2 trial. 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