{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:56:21Z","timestamp":1790290581656,"version":"4.1.0"},"reference-count":70,"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":[[2005,5]]},"abstract":"<jats:p>Host immune responses to commensal flora and enteric pathogens are known to influence gene expression in the intestinal epithelium. Although the Cdx family of caudal-related transcription factors represents critical regulators of gene expression in the intestinal epithelium, the effect of intestinal immune responses on Cdx expression and function has not been determined. We have shown that bacterial colonization and Th2 immune stimulation by intestinal nematode infection induce expression of the intestinal goblet cell-specific gene RELM\u03b2. In this study, we investigated the transcriptional regulation of resistin-like molecule\/found in inflammatory zone (RELM\/FIZZ, RELM\u03b2) and its isoforms RELM\u03b1 and RELM\u03b3 to ascertain the role of Cdx in modifying intestinal gene expression associated with innate and adaptive immune responses. Analysis of the RELM\u03b2 promoter showed that Cdx2 plays a critical role in basal gene activation in vitro. This was confirmed in vivo using transgenic mice, where ectopic gastric and hepatic expression of Cdx2 induces expression of RELM\u03b2, but not RELM\u03b1 or RELM\u03b3, exclusively in the stomach. Although there was no quantitative change in colonic Cdx2 mRNA expression, protein distribution, or phosphorylation of Cdx2, bacterial colonization induced expression of RELM\u03b2, but not RELM\u03b1 or RELM\u03b3. In contrast, parasitic nematode infections activated colonic expression of all three RELM isoforms without alteration in Cdx2 expression. These results demonstrated that Cdx2 participates in directing intestine-specific expression of RELM\u03b2 in the presence of commensal bacteria and that adaptive Th2 immune responses to intestinal nematode infections can activate intestinal goblet cell-specific gene expression independent of Cdx2.<\/jats:p>","DOI":"10.1152\/ajpgi.00442.2004","type":"journal-article","created":{"date-parts":[[2004,12,3]],"date-time":"2004-12-03T01:31:01Z","timestamp":1102037461000},"page":"G1074-G1083","source":"Crossref","is-referenced-by-count":36,"title":["Regulation of RELM\/FIZZ isoform expression by<i>Cdx2<\/i>in response to innate and adaptive immune stimulation in the intestine"],"prefix":"10.1152","volume":"288","author":[{"given":"Mei-Lun","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus E.","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela A.","family":"Knight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Artis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra G.","family":"Silberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunran","family":"Suh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary D.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0950fje"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1038\/90609"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.8.4481"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404034101"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200007)30:7<2083::AID-IMMU2083>3.0.CO;2-3"},{"key":"R6","doi-asserted-by":"crossref","unstructured":"Bancroft AJ, McKenzie AN, and Grencis RK.A critical role for IL-13 in resistance to intestinal nematode infection.J Immunol160: 3453\u20133461, 1998.","DOI":"10.4049\/jimmunol.160.7.3453"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103109200"},{"key":"R8","doi-asserted-by":"crossref","unstructured":"Beagley KWand Elson CO.Cells and cytokines in mucosal immunity and inflammation.Gastroenterol Clin North Am21: 347\u2013366, 1992.","DOI":"10.1016\/S0889-8553(21)00035-2"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1136\/gut.51.3.450"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401654101"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.16.10689"},{"key":"R12","unstructured":"Correa Pand Shiao YH.Phenotypic and genotypic events in gastric carcinogenesis.Cancer Res54: 1, 1941."},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1084\/jem.181.2.537"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204645"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206352"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1007\/s005350300001"},{"key":"R17","unstructured":"Ee HC, Erler T, Bhathal PS, Young GP, and James RJ.Cdx-2 homeodomain protein expression in human and rat colorectal adenoma and carcinoma.Am J Pathol147: 586\u2013592, 1995."},{"key":"R18","unstructured":"Falk PG, Hooper LV, Midtvedt T, and Gordon JI.Creating and maintaining the gastrointestinal ecosystem: what we know and need to know from gnotobiology.Microbiol Mol Biol Rev62: 1157\u20131170, 1998."},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910570306"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1139\/o99-001"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastro.2003.07.009"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200324264"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2003.1333"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307435200"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307435200"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.36598"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63074-X"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.15.4046"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1038\/ni888"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.17.9833"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1159\/000146301"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1997.v113.pm9247474"},{"key":"R33","doi-asserted-by":"crossref","unstructured":"James R, Erler T, and Kazenwadel J.Structure of the murine homeobox gene cdx-2. Expression in embryonic and adult intestinal epithelium.J Biol Chem269: 15229\u201315237, 1994.","DOI":"10.1016\/S0021-9258(17)36596-1"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3024.2001.00353.x"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64236-8"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.12.1849"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-3-7"},{"key":"R38","doi-asserted-by":"crossref","unstructured":"Lorentz O, Duluc I, Arcangelis AD, Simon-Assmann P, Kedinger M, and Freund JN.Key role of the Cdx2 homeobox gene in extracellular matrix-mediated intestinal cell differentiation.J Cell Biol139: 1553\u20131565, 1553.","DOI":"10.1083\/jcb.139.6.1553"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.139.6.1553"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206770"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.8.4417"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19970220)74:1<35::AID-IJC7>3.0.CO;2-1"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00338"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(98)70134-4"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309019200"},{"key":"R46","doi-asserted-by":"crossref","unstructured":"Meyer BIand Gruss P.Mouse Cdx-1 expression during gastrulation.Development117: 191\u2013203, 1993.","DOI":"10.1242\/dev.117.1.191"},{"key":"R47","doi-asserted-by":"crossref","unstructured":"Monaghan AP, Kaestner KH, Grau E, and Schutz G.Postimplantation expression patterns indicate a role for the mouse forkhead\/HNF-3 \u03b1, \u03b2 and \u03b3 genes in determination of the definitive endoderm, chordamesoderm and neuroectoderm.Development119: 567\u2013578, 1993.","DOI":"10.1242\/dev.119.3.567"},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1997.tb00966.x"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)00480-1"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200311000-00006"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.1136\/gut.51.2.184"},{"key":"R52","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.29618"},{"key":"R53","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110261200"},{"key":"R54","doi-asserted-by":"publisher","DOI":"10.1038\/ni712"},{"key":"R55","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.31902"},{"key":"R56","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.18142"},{"key":"R57","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.18142"},{"key":"R58","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70283-0"},{"key":"R59","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.4.1789"},{"key":"R60","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.11.7340"},{"key":"R61","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.2.619"},{"key":"R62","doi-asserted-by":"publisher","DOI":"10.1089\/dna.1997.16.1419"},{"key":"R63","doi-asserted-by":"publisher","DOI":"10.1007\/BF02814746"},{"key":"R64","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.58.030196.001423"},{"key":"R65","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.12.8.3614"},{"key":"R66","doi-asserted-by":"crossref","unstructured":"Van den Akker E, Forlani S, Chawengsaksophak K, de Graaff W, Beck F, Meyer BI, and Deschamps J.Cdx1 and Cdx2 have overlapping functions in anteroposterior patterning and posterior axis elongation.Development129: 2181\u20132193, 2002.","DOI":"10.1242\/dev.129.9.2181"},{"key":"R67","doi-asserted-by":"publisher","DOI":"10.1136\/gut.51.3.301"},{"key":"R68","doi-asserted-by":"crossref","unstructured":"Wu GD, Chen L, Forslund K, and Traber PG.Hepatocyte nuclear factor-1\u03b1 (HNF-1\u03b1) and HNF-1\u03b2 regulate transcription via two elements in an intestine-specific promoter.J Biol Chem269: 17080\u201317085, 1994.","DOI":"10.1016\/S0021-9258(17)32523-1"},{"key":"R69","doi-asserted-by":"crossref","unstructured":"Wu GD, Wang W, and Traber PG.Isolation and characterization of the human sucrase-isomaltase gene and demonstration of intestine-specific transcriptional elements.J Biol Chem267: 7863\u20137870, 1992.","DOI":"10.1016\/S0021-9258(18)42593-8"},{"key":"R70","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02935-2"}],"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.00442.2004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,30]],"date-time":"2023-04-30T17:34:44Z","timestamp":1682876084000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpgi.00442.2004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,5]]},"references-count":70,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2005,5]]}},"alternative-id":["10.1152\/ajpgi.00442.2004"],"URL":"https:\/\/doi.org\/10.1152\/ajpgi.00442.2004","relation":{},"ISSN":["0193-1857","1522-1547"],"issn-type":[{"value":"0193-1857","type":"print"},{"value":"1522-1547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,5]]}}}