{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:16:50Z","timestamp":1791217010321,"version":"4.1.0"},"reference-count":80,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,3,12]]},"abstract":"<jats:p>The molecular mechanisms that drive mucosal T helper type 2 (TH2) responses against parasitic helminths and allergens remain unclear. In this study, we demonstrate in mice that TFF2 (trefoil factor 2), an epithelial cell\u2013derived repair molecule, is needed for the control of lung injury caused by the hookworm parasite Nippostrongylus brasiliensis and for type 2 immunity after infection. TFF2 is also necessary for the rapid production of IL-33, a TH2-promoting cytokine, by lung epithelia, alveolar macrophages, and inflammatory dendritic cells in infected mice. TFF2 also increases the severity of allergic lung disease caused by house dust mite antigens or IL-13. Moreover, TFF2 messenger RNA expression is significantly increased in nasal mucosal brushings during asthma exacerbations in children. These experiments extend the biological functions of TFF2 from tissue repair to the initiation and maintenance of mucosal TH2 responses.<\/jats:p>","DOI":"10.1084\/jem.20110079","type":"journal-article","created":{"date-parts":[[2012,2,13]],"date-time":"2012-02-13T23:45:52Z","timestamp":1329176752000},"page":"607-622","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":183,"title":["Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection"],"prefix":"10.1084","volume":"209","author":[{"given":"Marsha","family":"Wills-Karp","sequence":"first","affiliation":[{"name":"Division of Immunobiology 1 and 2"},{"name":"Division of Asthma Research, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Rani","sequence":"additional","affiliation":[{"name":"Division of Immunobiology 1 and 2"},{"name":"Division of Asthma Research, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista","family":"Dienger","sequence":"additional","affiliation":[{"name":"Division of Immunobiology 1 and 2"},{"name":"Division of Asthma Research, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Lewkowich","sequence":"additional","affiliation":[{"name":"Division of Immunobiology 1 and 2"},{"name":"Division of Asthma Research, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James G.","family":"Fox","sequence":"additional","affiliation":[{"name":"Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Perkins","sequence":"additional","affiliation":[{"name":"Division of Immunobiology 1 and 2"},{"name":"Division of Asthma Research, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Immunobiology 1 and 2"},{"name":"Division of Asthma Research, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred D.","family":"Finkelman","sequence":"additional","affiliation":[{"name":"Division of Immunobiology 1 and 2"},{"name":"Division of Asthma Research, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229 1 and 2"},{"name":"Division of Immunology, Allergy, and Rheumatology, University of Cincinnati College of Medicine, Cincinnati, OH 45267 4"},{"name":"Department of Medicine, Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45220 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk E.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Inflammation Research, Amgen, Seattle, WA 98119 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Bryce","sequence":"additional","affiliation":[{"name":"Division of Allergy\u2013Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn A.","family":"Kurt-Jones","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655 8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy C.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Columbia University Medical Center, New York, NY 10032 9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umasundari","family":"Sivaprasad","sequence":"additional","affiliation":[{"name":"Division of Immunobiology 1 and 2"},{"name":"Division of Asthma Research, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurjit K.","family":"Hershey","sequence":"additional","affiliation":[{"name":"Division of Immunobiology 1 and 2"},{"name":"Division of Asthma Research, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De\u2019Broski R.","family":"Herbert","sequence":"additional","affiliation":[{"name":"Division of Immunobiology 1 and 2"},{"name":"Division of Asthma Research, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2012,2,13]]},"reference":[{"key":"2023072601055702800_bib1","doi-asserted-by":"publisher","first-page":"188","DOI":"10.2174\/187221307782418865","article-title":"Novel approaches for inhibition of mucus hypersecretion in asthma","volume":"1","author":"Agrawal","year":"2007","journal-title":"Recent Pat. Inflamm. Allergy Drug Discov."},{"key":"2023072601055702800_bib2","doi-asserted-by":"publisher","first-page":"18660","DOI":"10.1073\/pnas.0705939104","article-title":"IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells","volume":"104","author":"Ali","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072601055702800_bib3","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1038\/ni1100","article-title":"Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5","volume":"5","author":"Allen","year":"2004","journal-title":"Nat. Immunol."},{"key":"2023072601055702800_bib4","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/mi.2008.21","article-title":"The intestinal epithelium: sensors to effectors in nematode infection","volume":"1","author":"Artis","year":"2008","journal-title":"Mucosal Immunol."},{"key":"2023072601055702800_bib5","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/s11882-001-0037-z","article-title":"The global burden of asthma and allergic diseases: the challenge for the new century","volume":"1","author":"Baena-Cagnani","year":"2001","journal-title":"Curr. Allergy Asthma Rep."},{"key":"2023072601055702800_bib6","doi-asserted-by":"publisher","first-page":"G723","DOI":"10.1152\/ajpgi.00414.2010","article-title":"Fibrosis is regulated by Th2 and Th17 responses and by dynamic interactions between fibroblasts and macrophages","volume":"300","author":"Barron","year":"2011","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"2023072601055702800_bib7","doi-asserted-by":"publisher","first-page":"4S","DOI":"10.1378\/chest.130.1_suppl.4S","article-title":"The global burden of asthma","volume":"130","author":"Braman","year":"2006","journal-title":"Chest."},{"key":"2023072601055702800_bib8","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.ajpath.2010.08.003","article-title":"Wound macrophages as key regulators of repair: origin, phenotype, and function","volume":"178","author":"Brancato","year":"2011","journal-title":"Am. J. Pathol."},{"key":"2023072601055702800_bib9","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1016\/j.ijpara.2010.04.004","article-title":"Estimating the global distribution and disease burden of intestinal nematode infections: adding up the numbers\u2014a review","volume":"40","author":"Brooker","year":"2010","journal-title":"Int. J. Parasitol."},{"key":"2023072601055702800_bib10","doi-asserted-by":"publisher","first-page":"e779","DOI":"10.1371\/journal.pntd.0000779","article-title":"The global atlas of helminth infection: mapping the way forward in neglected tropical disease control","volume":"4","author":"Brooker","year":"2010","journal-title":"PLoS Negl. Trop. Dis."},{"key":"2023072601055702800_bib11","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1073\/pnas.0606854104","article-title":"IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo","volume":"104","author":"Carriere","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072601055702800_bib12","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1038\/ni.2045","article-title":"Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity","volume":"12","author":"Chang","year":"2011","journal-title":"Nat. Immunol."},{"key":"2023072601055702800_bib13","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1084\/jem.190.7.895","article-title":"Crucial role of the interleukin 1 receptor family member T1\/ST2 in T helper cell type 2\u2013mediated lung mucosal immune responses","volume":"190","author":"Coyle","year":"1999","journal-title":"J. Exp. Med."},{"key":"2023072601055702800_bib14","doi-asserted-by":"publisher","first-page":"3650","DOI":"10.1074\/jbc.M804935200","article-title":"Secreted trefoil factor 2 activates the CXCR4 receptor in epithelial and lymphocytic cancer cell lines","volume":"284","author":"Dubeykovskaya","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2023072601055702800_bib15","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1084\/jem.20051615","article-title":"Identification of an interleukin (IL)-25\u2013dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion","volume":"203","author":"Fallon","year":"2006","journal-title":"J. Exp. Med."},{"key":"2023072601055702800_bib16","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1172\/JCI0212529","article-title":"TFF2\/SP-deficient mice show decreased gastric proliferation, increased acid secretion, and increased susceptibility to NSAID injury","volume":"109","author":"Farrell","year":"2002","journal-title":"J. Clin. Invest."},{"key":"2023072601055702800_bib17","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1093\/intimm\/11.11.1811","article-title":"Development of an assay to measure in vivo cytokine production in the mouse","volume":"11","author":"Finkelman","year":"1999","journal-title":"Int. Immunol."},{"key":"2023072601055702800_bib18","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.4049\/jimmunol.151.3.1235","article-title":"Anti-cytokine antibodies as carrier proteins. Prolongation of in vivo effects of exogenous cytokines by injection of cytokine-anti-cytokine antibody complexes","volume":"151","author":"Finkelman","year":"1993","journal-title":"J. Immunol."},{"key":"2023072601055702800_bib19","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1111\/j.0105-2896.2004.00192.x","article-title":"Interleukin-4- and interleukin-13-mediated host protection against intestinal nematode parasites","volume":"201","author":"Finkelman","year":"2004","journal-title":"Immunol. Rev."},{"key":"2023072601055702800_bib20","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/sj.tpj.6500357","article-title":"Gene expression analysis in a murine model of allergic asthma reveals overlapping disease and therapy dependent pathways in the lung","volume":"6","author":"Follettie","year":"2006","journal-title":"Pharmacogenomics J."},{"key":"2023072601055702800_bib21","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.2353\/ajpath.2007.070249","article-title":"Accelerated progression of gastritis to dysplasia in the pyloric antrum of TFF2\u2212\/\u2212 C57BL6 x Sv129 Helicobacter pylori-infected mice","volume":"171","author":"Fox","year":"2007","journal-title":"Am. J. Pathol."},{"key":"2023072601055702800_bib22","doi-asserted-by":"crossref","first-page":"499","DOI":"10.4049\/jimmunol.165.1.499","article-title":"Critical involvement of the chemotactic axis CXCR4\/stromal cell-derived factor-1 alpha in the inflammatory component of allergic airway disease","volume":"165","author":"Gonzalo","year":"2000","journal-title":"J. Immunol."},{"key":"2023072601055702800_bib23","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/6565","article-title":"CCR5- and CXCR4-tropic HIV-1 are equally cytopathic for their T-cell targets in human lymphoid tissue","volume":"5","author":"Grivel","year":"1999","journal-title":"Nat. Med."},{"key":"2023072601055702800_bib24","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.jaci.2004.10.032","article-title":"Altered gene expression profiles in nasal respiratory epithelium reflect stable versus acute childhood asthma","volume":"115","author":"Guajardo","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"2023072601055702800_bib25","doi-asserted-by":"publisher","first-page":"13463","DOI":"10.1073\/pnas.0906988106","article-title":"IL-1 family members and STAT activators induce cytokine production by Th2, Th17, and Th1 cells","volume":"106","author":"Guo","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072601055702800_bib26","doi-asserted-by":"publisher","first-page":"2097","DOI":"10.1084\/jem.20101563","article-title":"Inflammatory dendritic cells\u2014not basophils\u2014are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen","volume":"207","author":"Hammad","year":"2010","journal-title":"J. Exp. Med."},{"key":"2023072601055702800_bib27","doi-asserted-by":"crossref","first-page":"7214","DOI":"10.4049\/jimmunol.181.10.7214","article-title":"IL-10 and TGF-\u03b2 redundantly protect against severe liver injury and mortality during acute schistosomiasis","volume":"181","author":"Herbert","year":"2008","journal-title":"J. Immunol."},{"key":"2023072601055702800_bib28","doi-asserted-by":"publisher","first-page":"2947","DOI":"10.1084\/jem.20091268","article-title":"Intestinal epithelial cell secretion of RELM-\u03b2 protects against gastrointestinal worm infection","volume":"206","author":"Herbert","year":"2009","journal-title":"J. Exp. Med."},{"key":"2023072601055702800_bib29","doi-asserted-by":"publisher","first-page":"6438","DOI":"10.4049\/jimmunol.0902009","article-title":"Arginase I suppresses IL-12\/IL-23p40-driven intestinal inflammation during acute schistosomiasis","volume":"184","author":"Herbert","year":"2010","journal-title":"J. Immunol."},{"key":"2023072601055702800_bib30","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1084\/jem.190.10.1541","article-title":"The absence of interleukin 1 receptor-related T1\/ST2 does not affect T helper cell type 2 development and its effector function","volume":"190","author":"Hoshino","year":"1999","journal-title":"J. Exp. Med."},{"key":"2023072601055702800_bib31","doi-asserted-by":"publisher","first-page":"e11944","DOI":"10.1371\/journal.pone.0011944","article-title":"IL-33 is produced by mast cells and regulates IgE-dependent inflammation","volume":"5","author":"Hsu","year":"2010","journal-title":"PLoS ONE."},{"key":"2023072601055702800_bib32","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.4049\/jimmunol.180.4.2443","article-title":"IL-33, a potent inducer of adaptive immunity to intestinal nematodes","volume":"180","author":"Humphreys","year":"2008","journal-title":"J. Immunol."},{"key":"2023072601055702800_bib33","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1084\/jem.20051135","article-title":"TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand","volume":"202","author":"Ito","year":"2005","journal-title":"J. Exp. Med."},{"key":"2023072601055702800_bib34","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.4049\/jimmunol.164.6.3047","article-title":"Single cell analysis reveals that IL-4 receptor\/Stat6 signaling is not required for the in vivo or in vitro development of CD4+ lymphocytes with a Th2 cytokine profile","volume":"164","author":"Jankovic","year":"2000","journal-title":"J. Immunol."},{"key":"2023072601055702800_bib35","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/j.jaci.2010.03.002","article-title":"Guilt by intimate association: what makes an allergen an allergen?","volume":"125","author":"Karp","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"2023072601055702800_bib36","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1164\/rccm.200805-666OC","article-title":"Resolution of allergic inflammation and airway hyperreactivity is dependent upon disruption of the T1\/ST2-IL-33 pathway","volume":"179","author":"Kearley","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2023072601055702800_bib37","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nm734","article-title":"Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma","volume":"8","author":"Kuperman","year":"2002","journal-title":"Nat. Med."},{"key":"2023072601055702800_bib38","doi-asserted-by":"crossref","first-page":"4780","DOI":"10.4049\/jimmunol.181.7.4780","article-title":"IL-33 induces antigen-specific IL-5+ T cells and promotes allergic-induced airway inflammation independent of IL-4","volume":"181","author":"Kurowska-Stolarska","year":"2008","journal-title":"J. Immunol."},{"key":"2023072601055702800_bib39","doi-asserted-by":"publisher","first-page":"6469","DOI":"10.4049\/jimmunol.0901575","article-title":"IL-33 amplifies the polarization of alternatively activated macrophages that contribute to airway inflammation","volume":"183","author":"Kurowska-Stolarska","year":"2009","journal-title":"J. Immunol."},{"key":"2023072601055702800_bib40","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1128\/IAI.02039-05","article-title":"Trefoil family factor 2 is expressed in murine gastric and immune cells and controls both gastrointestinal inflammation and systemic immune responses","volume":"75","author":"Kurt-Jones","year":"2007","journal-title":"Infect. Immun."},{"key":"2023072601055702800_bib41","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1016\/j.immuni.2009.08.008","article-title":"Biology of lung dendritic cells at the origin of asthma","volume":"31","author":"Lambrecht","year":"2009","journal-title":"Immunity."},{"key":"2023072601055702800_bib42","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1084\/jem.20051506","article-title":"CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function","volume":"202","author":"Lewkowich","year":"2005","journal-title":"J. Exp. Med."},{"key":"2023072601055702800_bib43","doi-asserted-by":"publisher","first-page":"6930","DOI":"10.1073\/pnas.95.12.6930","article-title":"T1\/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function","volume":"95","author":"L\u00f6hning","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072601055702800_bib44","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1016\/S0002-9440(10)62562-X","article-title":"AMD3100, a CxCR4 antagonist, attenuates allergic lung inflammation and airway hyperreactivity","volume":"160","author":"Lukacs","year":"2002","journal-title":"Am. J. Pathol."},{"key":"2023072601055702800_bib45","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1002\/eji.200737827","article-title":"Nippostrongylus brasiliensis infection leads to the development of emphysema associated with the induction of alternatively activated macrophages","volume":"38","author":"Marsland","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"2023072601055702800_bib46","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1111\/j.2042-3306.1998.tb04098.x","article-title":"Quantification of exercise-induced pulmonary haemorrhage with bronchoalveolar lavage","volume":"30","author":"Meyer","year":"1998","journal-title":"Equine Vet. J."},{"key":"2023072601055702800_bib47","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/S1074-7613(01)00186-8","article-title":"Analysis of type 2 immunity in vivo with a bicistronic IL-4 reporter","volume":"15","author":"Mohrs","year":"2001","journal-title":"Immunity."},{"key":"2023072601055702800_bib48","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.4049\/jimmunol.177.3.1393","article-title":"Novel effector molecules in type 2 inflammation: lessons drawn from helminth infection and allergy","volume":"177","author":"Nair","year":"2006","journal-title":"J. Immunol."},{"key":"2023072601055702800_bib49","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1038\/nature08900","article-title":"Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity","volume":"464","author":"Neill","year":"2010","journal-title":"Nature."},{"key":"2023072601055702800_bib50","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1165\/rcmb.2002-0309OC","article-title":"Trefoil factor-2 is an allergen-induced gene regulated by Th2 cytokines and STAT6 in the lung","volume":"29","author":"Nikolaidis","year":"2003","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2023072601055702800_bib51","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1080\/01902140601059547","article-title":"Allergen induced TFF2 is expressed by mucus-producing airway epithelial cells but is not a major regulator of inflammatory responses in the murine lung","volume":"32","author":"Nikolaidis","year":"2006","journal-title":"Exp. Lung Res."},{"key":"2023072601055702800_bib52","doi-asserted-by":"publisher","first-page":"18581","DOI":"10.1073\/pnas.1003059107","article-title":"IL-33 is a crucial amplifier of innate rather than acquired immunity","volume":"107","author":"Oboki","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072601055702800_bib53","doi-asserted-by":"publisher","first-page":"7890","DOI":"10.4049\/jimmunol.0802449","article-title":"Caspase-1, caspase-8, and calpain are dispensable for IL-33 release by macrophages","volume":"183","author":"Ohno","year":"2009","journal-title":"J. Immunol."},{"key":"2023072601055702800_bib54","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S1074-7613(00)80156-9","article-title":"Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment","volume":"12","author":"Ouyang","year":"2000","journal-title":"Immunity."},{"key":"2023072601055702800_bib55","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/nri2735","article-title":"How are TH2-type immune responses initiated and amplified?","volume":"10","author":"Paul","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"2023072601055702800_bib56","doi-asserted-by":"publisher","first-page":"13418","DOI":"10.1074\/jbc.M800177200","article-title":"Intestinal trefoil factor\/TFF3 promotes re-epithelialization of corneal wounds","volume":"283","author":"Paulsen","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2023072601055702800_bib57","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1182\/blood-2008-05-157818","article-title":"Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33","volume":"113","author":"Pecaric-Petkovic","year":"2009","journal-title":"Blood."},{"key":"2023072601055702800_bib58","doi-asserted-by":"publisher","first-page":"2089","DOI":"10.1084\/jem.20100734","article-title":"CD11c depletion severely disrupts Th2 induction and development in vivo","volume":"207","author":"Phythian-Adams","year":"2010","journal-title":"J. Exp. Med."},{"key":"2023072601055702800_bib59","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1007\/BF01213309","article-title":"Healing the epithelium: solving the problem from two sides","volume":"32","author":"Podolsky","year":"1997","journal-title":"J. Gastroenterol."},{"key":"2023072601055702800_bib60","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.regpep.2004.09.007","article-title":"Luminal and parenteral TFF2 and TFF3 dimer and monomer in two models of experimental colitis in the rat","volume":"126","author":"Poulsen","year":"2005","journal-title":"Regul. Pept."},{"key":"2023072601055702800_bib61","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1016\/j.jaci.2009.12.935","article-title":"Increased IL-33 expression by epithelial cells in bronchial asthma","volume":"125","author":"Pr\u00e9fontaine","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"2023072601055702800_bib62","doi-asserted-by":"publisher","first-page":"9773","DOI":"10.1073\/pnas.0901206106","article-title":"The cytokine interleukin-33 mediates anaphylactic shock","volume":"106","author":"Pushparaj","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072601055702800_bib63","doi-asserted-by":"publisher","first-page":"2000","DOI":"10.1002\/eji.201041135","article-title":"TGF-\u03b2 limits IL-33 production and promotes the resolution of colitis through regulation of macrophage function","volume":"41","author":"Rani","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"2023072601055702800_bib64","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1016\/j.jaci.2009.02.026","article-title":"IL-33-activated dendritic cells induce an atypical TH2-type response","volume":"123","author":"Rank","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"2023072601055702800_bib65","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.4049\/jimmunol.0903306","article-title":"IL-33 induces IL-13-dependent cutaneous fibrosis","volume":"184","author":"Rankin","year":"2010","journal-title":"J. Immunol."},{"key":"2023072601055702800_bib66","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1038\/nature08901","article-title":"IL25 elicits a multipotent progenitor cell population that promotes TH2 cytokine responses","volume":"464","author":"Saenz","year":"2010","journal-title":"Nature."},{"key":"2023072601055702800_bib67","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/j.immuni.2005.09.015","article-title":"IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines","volume":"23","author":"Schmitz","year":"2005","journal-title":"Immunity."},{"key":"2023072601055702800_bib68","doi-asserted-by":"crossref","first-page":"6158","DOI":"10.4049\/jimmunol.172.10.6158","article-title":"IL-4-induced GATA-3 expression is a time-restricted instruction switch for Th2 cell differentiation","volume":"172","author":"Seki","year":"2004","journal-title":"J. Immunol."},{"key":"2023072601055702800_bib69","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/978-3-642-59430-4_10","article-title":"MyD88 as a bottle neck in Toll\/IL-1 signaling","volume":"270","author":"Takeuchi","year":"2002","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"2023072601055702800_bib70","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1038\/nrm1203","article-title":"Trefoil factors: initiators of mucosal healing","volume":"4","author":"Taupin","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2023072601055702800_bib71","doi-asserted-by":"publisher","first-page":"R31","DOI":"10.1172\/JCI3304","article-title":"The trefoil gene family are coordinately expressed immediate-early genes: EGF receptor- and MAP kinase-dependent interregulation","volume":"103","author":"Taupin","year":"1999","journal-title":"J. Clin. Invest."},{"key":"2023072601055702800_bib72","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1046\/j.1365-2362.2002.01014.x","article-title":"Effect of trefoil factors on the viscoelastic properties of mucus gels","volume":"32","author":"Thim","year":"2002","journal-title":"Eur. J. Clin. Invest."},{"key":"2023072601055702800_bib73","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1084\/jem.191.6.1069","article-title":"T1\/ST2-deficient mice demonstrate the importance of T1\/ST2 in developing primary T helper cell type 2 responses","volume":"191","author":"Townsend","year":"2000","journal-title":"J. Exp. Med."},{"key":"2023072601055702800_bib74","doi-asserted-by":"publisher","first-page":"386","DOI":"10.2353\/ajpath.2007.070152","article-title":"Epithelial cell adhesion molecule: more than a carcinoma marker and adhesion molecule","volume":"171","author":"Trzpis","year":"2007","journal-title":"Am. J. Pathol."},{"key":"2023072601055702800_bib75","doi-asserted-by":"publisher","first-page":"12423","DOI":"10.1073\/pnas.0806372105","article-title":"In vivo studies fail to reveal a role for IL-4 or STAT6 signaling in Th2 lymphocyte differentiation","volume":"105","author":"van Panhuys","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072601055702800_bib76","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1084\/jem.20042311","article-title":"In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma","volume":"201","author":"van Rijt","year":"2005","journal-title":"J. Exp. Med."},{"key":"2023072601055702800_bib77","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1084\/jem.20052448","article-title":"Type 2 immunity is controlled by IL-4\/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system","volume":"203","author":"Voehringer","year":"2006","journal-title":"J. Exp. Med."},{"key":"2023072601055702800_bib78","doi-asserted-by":"publisher","first-page":"2258","DOI":"10.1126\/science.282.5397.2258","article-title":"Interleukin-13: central mediator of allergic asthma","volume":"282","author":"Wills-Karp","year":"1998","journal-title":"Science."},{"key":"2023072601055702800_bib79","doi-asserted-by":"publisher","first-page":"6097","DOI":"10.4049\/jimmunol.1003487","article-title":"IL-33 shifts the balance from osteoclast to alternatively activated macrophage differentiation and protects from TNF-alpha-mediated bone loss","volume":"186","author":"Zaiss","year":"2011","journal-title":"J. Immunol."},{"key":"2023072601055702800_bib80","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1038\/nature05590","article-title":"Epithelial-cell-intrinsic IKK-\u03b2 expression regulates intestinal immune homeostasis","volume":"446","author":"Zaph","year":"2007","journal-title":"Nature."}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/209\/3\/607\/1744693\/jem_20110079.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/209\/3\/607\/1744693\/jem_20110079.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T21:06:41Z","timestamp":1690319201000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/209\/3\/607\/41312\/Trefoil-factor-2-rapidly-induces-interleukin-33-to"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,13]]},"references-count":80,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2012,3,12]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20110079","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.13985973.15778094","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.13985973.15768250","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.13985973.792502928","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.13985973.15442063","asserted-by":"object"}]},"ISSN":["1540-9538","0022-1007"],"issn-type":[{"value":"1540-9538","type":"electronic"},{"value":"0022-1007","type":"print"}],"subject":[],"published":{"date-parts":[[2012,2,13]]}}}