{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Pyon GC"],"funding":["NIDDK NIH HHS","NIAID NIH HHS","NHLBI NIH HHS","NIH"],"pagination":["1545-1553.e2"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11625005"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["154(6)"],"pubmed_abstract":["<h4>Background</h4>IL-33 is a type 2 inflammatory cytokine that is elevated in the esophageal epithelium of eosinophilic esophagitis (EoE) subjects. We previously developed a mouse model of EoE dependent on constitutive overexpression of IL-33 from the esophageal epithelium (EoE33).<h4>Objective</h4>Our objective was to develop an inducible, IL-33-dependent model of EoE and examine induction of EoE-associated pathology.<h4>Methods</h4>We utilized a tetracycline-inducible system to express IL-33 in the esophagus by generating 2 transgenic mice. The first (iSophagus) expresses a reverse tetracycline transactivator from the esophageal epithelium. The second (TRE33) features a tetracycline response element driving expression of IL-33. When crossed, these mice generate an inducible model of EoE (iEoE33). Mice were administered doxycycline-infused chow for up to 2 weeks. Cytokines were assessed by ELISA or bead-based multiplex analysis. T cells were assessed by flow cytometry. Pathology was assessed by histology and immunohistochemistry for IL-33, eosinophil peroxidase, CD4, and Ki-67. iEoE33 was treated with steroids and crossed with IL-13<sup>-/-</sup> mice.<h4>Results</h4>Doxycycline-treated iEoE33 mice demonstrated expression of IL-33 in the esophageal epithelium, and esophageal pathology including eosinophilia, CD4<sup>+</sup> cell infiltrate, basal zone hyperplasia, and dilated intercellular spaces. These findings became pronounced on day 7 of induction, were accompanied by weight loss and esophageal thickening, and were steroid responsive and IL-13 dependent.<h4>Conclusion</h4>Inducible IL-33 expression in the esophageal epithelium elicited features pathognomonic of EoE. iEoE33 enables investigation of EoE disease mechanisms as well as initiation, progression, and resolution."],"journal":["The Journal of allergy and clinical immunology"],"pubmed_title":["Tissue-specific inducible IL-33 expression elicits features of eosinophilic esophagitis."],"pmcid":["PMC11625005"],"funding_grant_id":["R01 DK114436","K23 AI158813","R37 AI071106","R01 AI128729","R01 HL117823"],"pubmed_authors":["Gibson JB","Dao AD","Wright BL","Doyle AD","Kita H","Luo H","Pai RK","Rank MA","Pyon GC","Nakagawa H","Putikova A","Masuda MY","Bonellos JJ","LeSuer WE","Garg S","Ortiz DR","Heiligenstein PL"],"additional_accession":[]},"is_claimable":false,"name":"Tissue-specific inducible IL-33 expression elicits features of eosinophilic esophagitis.","description":"<h4>Background</h4>IL-33 is a type 2 inflammatory cytokine that is elevated in the esophageal epithelium of eosinophilic esophagitis (EoE) subjects. We previously developed a mouse model of EoE dependent on constitutive overexpression of IL-33 from the esophageal epithelium (EoE33).<h4>Objective</h4>Our objective was to develop an inducible, IL-33-dependent model of EoE and examine induction of EoE-associated pathology.<h4>Methods</h4>We utilized a tetracycline-inducible system to express IL-33 in the esophagus by generating 2 transgenic mice. The first (iSophagus) expresses a reverse tetracycline transactivator from the esophageal epithelium. The second (TRE33) features a tetracycline response element driving expression of IL-33. When crossed, these mice generate an inducible model of EoE (iEoE33). Mice were administered doxycycline-infused chow for up to 2 weeks. Cytokines were assessed by ELISA or bead-based multiplex analysis. T cells were assessed by flow cytometry. Pathology was assessed by histology and immunohistochemistry for IL-33, eosinophil peroxidase, CD4, and Ki-67. iEoE33 was treated with steroids and crossed with IL-13<sup>-/-</sup> mice.<h4>Results</h4>Doxycycline-treated iEoE33 mice demonstrated expression of IL-33 in the esophageal epithelium, and esophageal pathology including eosinophilia, CD4<sup>+</sup> cell infiltrate, basal zone hyperplasia, and dilated intercellular spaces. These findings became pronounced on day 7 of induction, were accompanied by weight loss and esophageal thickening, and were steroid responsive and IL-13 dependent.<h4>Conclusion</h4>Inducible IL-33 expression in the esophageal epithelium elicited features pathognomonic of EoE. iEoE33 enables investigation of EoE disease mechanisms as well as initiation, progression, and resolution.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2026-06-05T20:40:25.927Z","creation":"2026-05-21T03:13:02.909Z"},"accession":"S-EPMC11625005","cross_references":{"pubmed":["39265877"],"doi":["10.1016/j.jaci.2024.08.026"]}}