{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:45:18Z","timestamp":1791222318768,"version":"4.1.0"},"reference-count":61,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2018,6,10]],"date-time":"2018-06-10T00:00:00Z","timestamp":1528588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jacionline.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Allergy and Clinical Immunology"],"published-print":{"date-parts":[[2019,2]]},"DOI":"10.1016\/j.jaci.2018.05.026","type":"journal-article","created":{"date-parts":[[2018,6,11]],"date-time":"2018-06-11T11:35:55Z","timestamp":1528716955000},"page":"577-590","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":184,"title":["Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation"],"prefix":"10.1016","volume":"143","author":[{"given":"Zala","family":"Jevnikar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rgen","family":"\u00d6stling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Ax","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Calv\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristofer","family":"Th\u00f6rn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Israelsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"\u00d6berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akul","family":"Singhania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie C.K.","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan J.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anoop","family":"Chauhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana R.","family":"Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"De Meulder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Loza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Baribaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Sterk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kian Fan","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yike","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Adcock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie","family":"Payne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbro","family":"Dahlen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Chanez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominick E.","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Krug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens M.","family":"Hohlfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Sandstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratko","family":"Djukanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy S.C.","family":"Hinks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Howarth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Outi","family":"Vaarala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen","family":"van Geest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henric","family":"Olsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.M.","family":"Adcock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Auffray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Bakke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.T.","family":"Bansal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Baribaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Bates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.H.","family":"Bel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Bigler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Bisgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.J.","family":"Boedigheimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"B\u00f8nnelykke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Brandsma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Brinkman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Bucchioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Burg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Bush","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Caruso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Chaiboonchoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Chanez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.K.","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.H.","family":"Compton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Corfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"D'Amico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.E.","family":"Dahlen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"De Meulder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Djukanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.J.","family":"Erpenbeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Erzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Fichtner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Fitch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.J.","family":"Fleming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Formaggio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.J.","family":"Fowler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Frey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Gahlemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Geiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Goss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Haughney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Hedlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.W.","family":"Hekking","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Higenbottam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.M.","family":"Hohlfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Holweg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Horv\u00e1th","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.J.","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Knowles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.J.","family":"Knox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Krug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Lefaudeux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.J.","family":"Loza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Manta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.G.","family":"Matthews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Mazein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Meiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.J.M.","family":"Middelveld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Miralpeix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Montuschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Mores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.S.","family":"Murray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Musial","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Myles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Pahus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Pandis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Pavlidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Postle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Powel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Pratic\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Riley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Rowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Sandstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.P.R.","family":"Schofield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Seibold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Selby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.E.","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Sigmund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Singer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.J.","family":"Skipp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.R.","family":"Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.J.","family":"Sterk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Thornton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.M.","family":"van Aalderen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"van Geest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Vestbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.H.","family":"Vissing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.H.","family":"Wagener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.S.","family":"Wagers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Weiszhart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.E.","family":"Wheelock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.J.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"suppl\u00a01","key":"10.1016\/j.jaci.2018.05.026_bib1","doi-asserted-by":"crossref","first-page":"S78","DOI":"10.1513\/AnnalsATS.201508-515MG","article-title":"Asthma was talking, but we weren't listening. Missed or ignored signals that have slowed treatment progress","volume":"13","author":"Fahy","year":"2016","journal-title":"Ann Am Thorac Soc"},{"key":"10.1016\/j.jaci.2018.05.026_bib2","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.it.2012.07.003","article-title":"Interleukin-6: from an inflammatory marker to a target for inflammatory diseases","volume":"33","author":"Rincon","year":"2012","journal-title":"Trends Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj20030407","article-title":"Principles of interleukin (IL)-6-type cytokine signalling and its regulation","volume":"374","author":"Heinrich","year":"2003","journal-title":"Biochem J"},{"key":"10.1016\/j.jaci.2018.05.026_bib4","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.smim.2013.11.002","article-title":"Interleukin-6: from basic biology to selective blockade of pro-inflammatory activities","volume":"26","author":"Scheller","year":"2014","journal-title":"Semin Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib5","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1517\/14728222.11.5.613","article-title":"The IL-6\/sIL-6R complex as a novel target for therapeutic approaches","volume":"11","author":"Rose-John","year":"2007","journal-title":"Expert Opin Ther Targets"},{"key":"10.1016\/j.jaci.2018.05.026_bib6","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1042\/bj3000281","article-title":"Soluble receptors for cytokines and growth factors: generation and biological function","volume":"300","author":"Rose-John","year":"1994","journal-title":"Biochem J"},{"key":"10.1016\/j.jaci.2018.05.026_bib7","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0165-2478(99)00040-1","article-title":"Generation of \u2018truncated\u2019 interleukin-6 receptor (IL-6R) mRNA by alternative splicing; a possible source of soluble IL-6R","volume":"68","author":"Holub","year":"1999","journal-title":"Immunol Lett"},{"key":"10.1016\/j.jaci.2018.05.026_bib8","doi-asserted-by":"crossref","first-page":"14804","DOI":"10.1074\/jbc.M111.229393","article-title":"Species specificity of ADAM10 and ADAM17 proteins in interleukin-6 (IL-6) trans-signaling and novel role of ADAM10 in inducible IL-6 receptor shedding","volume":"286","author":"Garbers","year":"2011","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jaci.2018.05.026_bib9","doi-asserted-by":"crossref","first-page":"44053","DOI":"10.1038\/srep44053","article-title":"Meprin metalloproteases generate biologically active soluble interleukin-6 receptor to induce trans-signaling","volume":"7","author":"Arnold","year":"2017","journal-title":"Sci Rep"},{"key":"10.1016\/j.jaci.2018.05.026_bib10","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1084\/jem.189.3.599","article-title":"C-reactive protein: a physiological activator of interleukin 6 receptor shedding","volume":"189","author":"Jones","year":"1999","journal-title":"J Exp Med"},{"key":"10.1016\/j.jaci.2018.05.026_bib11","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S1074-7613(01)00151-0","article-title":"Il-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation","volume":"14","author":"Hurst","year":"2001","journal-title":"Immunity"},{"key":"10.1016\/j.jaci.2018.05.026_bib12","doi-asserted-by":"crossref","first-page":"7882","DOI":"10.1073\/pnas.93.15.7882","article-title":"Pore-forming toxins trigger shedding of receptors for interleukin 6 and lipopolysaccharide","volume":"93","author":"Walev","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.jaci.2018.05.026_bib13","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1189\/jlb.3A0515-207R","article-title":"ADAM17 controls IL-6 signaling by cleavage of the murine IL-6R\u03b1 from the cell surface of leukocytes during inflammatory responses","volume":"99","author":"Yan","year":"2016","journal-title":"J Leukoc Biol"},{"key":"10.1016\/j.jaci.2018.05.026_bib14","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1093\/hmg\/ddx053","article-title":"Neutrophil-mediated IL-6 receptor trans-signaling and the risk of chronic obstructive pulmonary disease and asthma","volume":"26","author":"Farahi","year":"2017","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.jaci.2018.05.026_bib15","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1164\/ajrccm.151.5.7735584","article-title":"Circulating interleukin-6 levels in patients with bronchial asthma","volume":"151","author":"Yokoyama","year":"1995","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2018.05.026_bib16","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1465-9921-11-28","article-title":"Elevation of IL-6 in the allergic asthmatic airway is independent of inflammation but associates with loss of central airway function","volume":"11","author":"Neveu","year":"2010","journal-title":"Respir Res"},{"key":"10.1016\/j.jaci.2018.05.026_bib17","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.3892\/etm.2016.3662","article-title":"FOXP3+ associated with the pro-inflammatory regulatory T and T helper 17 effector cells in asthma patients","volume":"12","author":"Zhang","year":"2016","journal-title":"Exp Ther Med"},{"key":"10.1016\/j.jaci.2018.05.026_bib18","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0091-6749(96)70014-3","article-title":"Inflammatory determinants of asthma severity: mediator and cellular changes in bronchoalveolar lavage fluid of patients with severe asthma","volume":"98","author":"Virchow","year":"1996","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib19","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/S2213-2600(16)30048-0","article-title":"Plasma interleukin-6 concentrations, metabolic dysfunction, and asthma severity: a cross-sectional analysis of two cohorts","volume":"4","author":"Peters","year":"2016","journal-title":"Lancet Respir Med"},{"key":"10.1016\/j.jaci.2018.05.026_bib20","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1164\/ajrccm.156.5.9610070","article-title":"Circulating levels of soluble interleukin-6 receptor in patients with bronchial asthma","volume":"156","author":"Yokoyama","year":"1997","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2018.05.026_bib21","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1172\/JCI200522433","article-title":"The IL-6R alpha chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in\u00a0vivo","volume":"115","author":"Doganci","year":"2005","journal-title":"J Clin Invest"},{"key":"10.1016\/j.jaci.2018.05.026_bib22","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jaci.2015.11.020","article-title":"Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3-like protein 1","volume":"138","author":"Hinks","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib23","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/S0140-6736(11)60874-X","article-title":"Identification of IL6R and chromosome 11q13.5 as risk loci for asthma","volume":"378","author":"Ferreira","year":"2011","journal-title":"Lancet"},{"key":"10.1016\/j.jaci.2018.05.026_bib24","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1183\/13993003.00779-2015","article-title":"Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort","volume":"46","author":"Shaw","year":"2015","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaci.2018.05.026_bib25","doi-asserted-by":"crossref","unstructured":"Woessner R, Bebernitz G, Bell K, Caccese R, Johnson N, Kettle J, et\u00a0al. Highly selective JAK1 kinase inhibitors suppress Y705-mediated STAT3 activation in a wide range of tumor types, with reduced hematological toxicity. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; April 6-10, 2013; Washington, DC. Cancer Res 2013;73(suppl):Abstract no. 931.","DOI":"10.1158\/1538-7445.AM2013-931"},{"key":"10.1016\/j.jaci.2018.05.026_bib26","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1183\/13993003.01129-2016","article-title":"Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study","volume":"48","author":"Wilson","year":"2016","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaci.2018.05.026_bib27","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1164\/rccm.201512-2452OC","article-title":"A transcriptome-driven analysis of epithelial brushings and bronchial biopsies to define asthma phenotypes in U-BIOPRED","volume":"195","author":"Kuo","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2018.05.026_bib28","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1016\/j.jaci.2016.08.048","article-title":"U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics","volume":"139","author":"Lefaudeux","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib29","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2165\/00151829-200403010-00003","article-title":"Matrix metalloproteinases in the pathogenesis of asthma and COPD: implications for therapy","volume":"3","author":"Suzuki","year":"2004","journal-title":"Treat Respir Med"},{"key":"10.1016\/j.jaci.2018.05.026_bib30","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.jaci.2013.03.003","article-title":"The chitinase-like protein YKL-40: a possible biomarker of inflammation and airway remodeling in severe pediatric asthma","volume":"132","author":"Konradsen","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib31","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1164\/rccm.200807-1081OC","article-title":"Osteopontin deficiency protects against airway remodeling and hyperresponsiveness in chronic asthma","volume":"179","author":"Simoes","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2018.05.026_bib32","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.jaci.2013.04.012","article-title":"IL-33 promotes airway remodeling in pediatric patients with severe steroid-resistant asthma","volume":"132","author":"Saglani","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib33","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1056\/NEJMoa073600","article-title":"A chitinase-like protein in the lung and circulation of patients with severe asthma","volume":"357","author":"Chupp","year":"2007","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jaci.2018.05.026_bib34","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1164\/ajrccm.159.4.9708080","article-title":"Contribution of 92 kDa gelatinase\/type IV collagenase in bronchial inflammation during status asthmaticus","volume":"159","author":"Lemjabbar","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2018.05.026_bib35","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1136\/thoraxjnl-2015-207428","article-title":"Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD","volume":"71","author":"Ostridge","year":"2016","journal-title":"Thorax"},{"key":"10.1016\/j.jaci.2018.05.026_bib36","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.4049\/jimmunol.1002568","article-title":"Gene expression patterns of Th2 inflammation and intercellular communication in asthmatic airways","volume":"186","author":"Choy","year":"2011","journal-title":"J Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib37","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.4161\/cbt.3.11.1172","article-title":"Genome-wide analysis of STAT target genes: elucidating the mechanism of STAT-mediated oncogenesis","volume":"3","author":"Alvarez","year":"2004","journal-title":"Cancer Biol Ther"},{"key":"10.1016\/j.jaci.2018.05.026_bib38","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1164\/rccm.200903-0392OC","article-title":"T-helper type 2-driven inflammation defines major subphenotypes of asthma","volume":"180","author":"Woodruff","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2018.05.026_bib39","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/cea.13085","article-title":"IL-6 pathway upregulation in subgroup of severe asthma is associated with neutrophilia and poor lung function","volume":"48","author":"Turan","year":"2018","journal-title":"Clin Exp Allergy"},{"key":"10.1016\/j.jaci.2018.05.026_bib40","doi-asserted-by":"crossref","first-page":"4956","DOI":"10.4049\/jimmunol.172.8.4956","article-title":"Triggering receptor expressed on myeloid cells-1 in neutrophil inflammatory responses: differential regulation of activation and survival","volume":"172","author":"Radsak","year":"2004","journal-title":"J Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib41","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.jaci.2015.01.014","article-title":"Innate and adaptive T cells in asthmatic patients: relationship to severity and disease mechanisms","volume":"136","author":"Hinks","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib42","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1165\/rcmb.2017-0162OC","article-title":"Multi-tissue transcriptomics delineates the diversity of airway T cell functions in asthma","volume":"58","author":"Singhania","year":"2018","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1016\/j.jaci.2018.05.026_bib43","doi-asserted-by":"crossref","first-page":"e0168680","DOI":"10.1371\/journal.pone.0168680","article-title":"Altered epithelial gene expression in peripheral airways of severe asthma","volume":"12","author":"Singhania","year":"2017","journal-title":"PLoS One"},{"key":"10.1016\/j.jaci.2018.05.026_bib44","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jaci.2014.06.035","article-title":"Biological clustering supports both \u201cDutch\u201d and \u201cBritish\u201d hypotheses of asthma and chronic obstructive pulmonary disease","volume":"135","author":"Ghebre","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib45","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/j.jaci.2008.04.005","article-title":"A novel IL-1 family cytokine, IL-33, potently activates human eosinophils","volume":"121","author":"Cherry","year":"2008","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib46","doi-asserted-by":"crossref","first-page":"3445","DOI":"10.4049\/jimmunol.1600611","article-title":"IL-33 precedes IL-5 in regulating eosinophil commitment and is required for eosinophil homeostasis","volume":"197","author":"Johnston","year":"2016","journal-title":"J Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib47","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/imm.12667","article-title":"Functional interleukin-33 receptors are expressed in early progenitor stages of allergy-related granulocytes","volume":"150","author":"Tsuzuki","year":"2017","journal-title":"Immunology"},{"key":"10.1016\/j.jaci.2018.05.026_bib48","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.jaci.2015.02.032","article-title":"Allergen-induced IL-6 trans-signaling activates \u03b3\u03b4 T cells to promote type 2 and type 17 airway inflammation","volume":"136","author":"Ullah","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib49","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13223-015-0081-1","article-title":"Therapeutic potential of anti-IL-6 therapies for granulocytic airway inflammation in asthma","volume":"11","author":"Chu","year":"2015","journal-title":"Allergy Asthma Clin Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib50","doi-asserted-by":"crossref","first-page":"9589","DOI":"10.1073\/pnas.0501794102","article-title":"IL-6 trans-signaling via STAT3 directs T cell infiltration in acute inflammation","volume":"102","author":"McLoughlin","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.jaci.2018.05.026_bib51","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1139\/Y08-004","article-title":"Altered expression of epithelial junctional proteins in atopic asthma: possible role in inflammation","volume":"86","author":"de Boer","year":"2008","journal-title":"Can J Physiol Pharmacol"},{"key":"10.1016\/j.jaci.2018.05.026_bib52","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.jaci.2011.05.038","article-title":"Defective epithelial barrier function in asthma","volume":"128","author":"Xiao","year":"2011","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib53","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jaci.2016.02.035","article-title":"Claudin-18 deficiency is associated with airway epithelial barrier dysfunction and asthma","volume":"139","author":"Sweerus","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib54","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1165\/rcmb.2013-0124OC","article-title":"Caveolin-1 controls airway epithelial barrier function. Implications for asthma","volume":"49","author":"Hackett","year":"2013","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1016\/j.jaci.2018.05.026_bib55","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nri3608","article-title":"Intestinal epithelial cells: regulators of barrier function and immune homeostasis","volume":"14","author":"Peterson","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib56","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/mi.2013.24","article-title":"MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C","volume":"7","author":"Corr","year":"2014","journal-title":"Mucosal Immunol"},{"key":"10.1016\/j.jaci.2018.05.026_bib57","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.chom.2011.04.012","article-title":"Invasive bacterial pathogens exploit TLR-mediated downregulation of tight junction components to facilitate translocation across the epithelium","volume":"9","author":"Clarke","year":"2011","journal-title":"Cell Host Microbe"},{"key":"10.1016\/j.jaci.2018.05.026_bib58","doi-asserted-by":"crossref","first-page":"e21827","DOI":"10.1371\/journal.pone.0021827","article-title":"Innate immune responses to bacterial ligands in the peripheral human lung\u2014role of alveolar epithelial TLR expression and signalling","volume":"6","author":"Thorley","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.jaci.2018.05.026_bib59","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.bjid.2015.10.011","article-title":"TLR2 and TLR4 mediated host immune responses in major infectious diseases: a review","volume":"20","author":"Mukherjee","year":"2016","journal-title":"Braz J Infect Dis"},{"key":"10.1016\/j.jaci.2018.05.026_bib60","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1136\/thorax.57.9.759","article-title":"Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations","volume":"57","author":"Patel","year":"2002","journal-title":"Thorax"},{"key":"10.1016\/j.jaci.2018.05.026_bib61","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1165\/ajrcmb.22.3.3690","article-title":"Airway hyperresponsiveness and airway obstruction in transgenic mice. Morphologic correlates in mice overexpressing interleukin (IL)-11 and IL-6 in the lung","volume":"22","author":"Kuhn","year":"2000","journal-title":"Am J Respir Cell Mol Biol"}],"container-title":["Journal of Allergy and Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0091674918308479?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0091674918308479?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T09:18:27Z","timestamp":1758791907000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0091674918308479"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2]]},"references-count":61,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["S0091674918308479"],"URL":"https:\/\/doi.org\/10.1016\/j.jaci.2018.05.026","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.733449703.793566480","asserted-by":"object"}]},"ISSN":["0091-6749"],"issn-type":[{"value":"0091-6749","type":"print"}],"subject":[],"published":{"date-parts":[[2019,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation","name":"articletitle","label":"Article Title"},{"value":"Journal of Allergy and Clinical Immunology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jaci.2018.05.026","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.","name":"copyright","label":"Copyright"}]}}