{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:45:30Z","timestamp":1778874330458,"version":"3.51.4"},"reference-count":41,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2014,9,1]]},"abstract":"<jats:p>Resistin-like molecule (Relm)-\u03b1 is a secreted, cysteine-rich protein belonging to a newly defined family of proteins, including resistin, Relm-\u03b2, and Relm-\u03b3. Although resistin was initially defined based on its insulin-resistance activity, the family members are highly induced in various inflammatory states. Earlier studies implicated Relm-\u03b1 in insulin resistance, asthmatic responses, and intestinal inflammation; however, its function still remains an enigma. We now report that Relm-\u03b1 is strongly induced in the esophagus in an allergen-challenged murine model of eosinophilic esophagitis (EoE). Furthermore, to understand the in vivo role of Relm-\u03b1, we generated Relm-\u03b1 gene-inducible bitransgenic mice by using lung-specific CC-10 promoter (CC10-rtTA- Relm-\u03b1). We found Relm-\u03b1 protein is significantly induced in the esophagus of CC10-rtTA- Relm-\u03b1 bitransgenic mice exposed to doxycycline food. The most prominent effect observed by the induction of Relm-\u03b1 is epithelial cell hyperplasia, basal layer thickness, accumulation of activated CD4<jats:sup>+<\/jats:sup>and CD4<jats:sup>\u2212<\/jats:sup>T cell subsets, and eosinophilic inflammation in the esophagus. The in vitro experiments further confirm that Relm-\u03b1 promotes primary epithelial cell proliferation but has no chemotactic activity for eosinophils. Taken together, our studies report for the first time that Relm-\u03b1 induction in the esophagus has a major role in promoting epithelial cell hyperplasia and basal layer thickness, and the accumulation of activated CD4<jats:sup>+<\/jats:sup>and CD4<jats:sup>\u2212<\/jats:sup>T cell subsets may be responsible for partial esophageal eosinophilia in the mouse models of EoE. Notably, the epithelial cell hyperplasia and basal layer thickness are the characteristic features commonly observed in human EoE.<\/jats:p>","DOI":"10.1152\/ajpgi.00141.2014","type":"journal-article","created":{"date-parts":[[2014,7,4]],"date-time":"2014-07-04T05:57:55Z","timestamp":1404453475000},"page":"G499-G507","source":"Crossref","is-referenced-by-count":15,"title":["Allergen-induced resistin-like molecule-\u03b1 promotes esophageal epithelial cell hyperplasia in eosinophilic esophagitis"],"prefix":"10.1152","volume":"307","author":[{"given":"Parm","family":"Mavi","sequence":"first","affiliation":[{"name":"University of Cincinnati College of Medicine, Cincinnati, Ohio;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rituraj","family":"Niranjan","sequence":"additional","affiliation":[{"name":"Allergy and Immunology, Cincinnati Children's Medical Center, Cincinnati, Ohio; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parmesh","family":"Dutt","sequence":"additional","affiliation":[{"name":"Section of Pulmonary Diseases, Department of Medicine, Tulane Eosinohilic Disorder Center, Tulane University School of Medicine, New Orleans, Louisiana;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asifa","family":"Zaidi","sequence":"additional","affiliation":[{"name":"Section of Pulmonary Diseases, Department of Medicine, Tulane Eosinohilic Disorder Center, Tulane University School of Medicine, New Orleans, Louisiana;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jai Shankar","family":"Shukla","sequence":"additional","affiliation":[{"name":"Section of Pulmonary Diseases, Department of Medicine, Tulane Eosinohilic Disorder Center, Tulane University School of Medicine, New Orleans, Louisiana;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Korfhagen","sequence":"additional","affiliation":[{"name":"Perinatal Institute, Cincinnati Children's Medical Center, Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anil","family":"Mishra","sequence":"additional","affiliation":[{"name":"Section of Pulmonary Diseases, Department of Medicine, Tulane Eosinohilic Disorder Center, Tulane University School of Medicine, New Orleans, Louisiana;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.06.027"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S1542-3565(04)00236-8"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103109200"},{"key":"B4","doi-asserted-by":"crossref","first-page":"RA55","DOI":"10.1484\/M.IMR-EB.3.658","volume":"9","author":"Beltowski J","year":"2003","journal-title":"Int Med J Exp Clin Res"},{"key":"B5","first-page":"19","volume":"19","author":"Blagoev B","year":"2002","journal-title":"J Biol Chem"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2001.790116.x"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2001.116436"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200102013440507"},{"key":"B9","author":"Cho JY","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.060617"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S0888-7543(03)00070-3"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastro.2003.07.009"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.157.1.9702074"},{"key":"B14","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.4049\/jimmunol.161.3.1501","volume":"161","author":"Hogan SP","year":"1998","journal-title":"J Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/86365"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2006.04.039"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2001.116002"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2004-0325OC"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.5.3425"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-13-51"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6273"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10224"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.5.2464"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6560"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastro.2003.07.007"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1106653"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00147.2007"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009481200"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0391OC"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1126\/science.1093466"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0304212"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8204"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00223.2011"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199201303260504"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020531322556"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.4.1789"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00442.2004"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.17.1.255"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.03.057"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17912"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000471"}],"container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpgi.00141.2014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,15]],"date-time":"2023-07-15T00:06:58Z","timestamp":1689379618000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpgi.00141.2014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,1]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2014,9,1]]}},"alternative-id":["10.1152\/ajpgi.00141.2014"],"URL":"https:\/\/doi.org\/10.1152\/ajpgi.00141.2014","relation":{},"ISSN":["0193-1857","1522-1547"],"issn-type":[{"value":"0193-1857","type":"print"},{"value":"1522-1547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,1]]}}}