biostudies-literaturePyon GCNIDDK NIH HHSNIAID NIH HHSNHLBI NIH HHSNIH1545-1553.e2https://www.ebi.ac.uk/biostudies/studies/S-EPMC11625005biostudies-literatureUnknown154(6)<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^-/- mice.<h4>Results</h4>Doxycycline-treated iEoE33 mice demonstrated expression of IL-33 in the esophageal epithelium, and esophageal pathology including eosinophilia, CD4⁺ 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.The Journal of allergy and clinical immunologyTissue-specific inducible IL-33 expression elicits features of eosinophilic esophagitis.PMC11625005R01 DK114436K23 AI158813R37 AI071106R01 AI128729R01 HL117823Gibson JBDao ADWright BLDoyle ADKita HLuo HPai RKRank MAPyon GCNakagawa HPutikova AMasuda MYBonellos JJLeSuer WEGarg SOrtiz DRHeiligenstein PLfalseTissue-specific inducible IL-33 expression elicits features of eosinophilic esophagitis.<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^-/- mice.<h4>Results</h4>Doxycycline-treated iEoE33 mice demonstrated expression of IL-33 in the esophageal epithelium, and esophageal pathology including eosinophilia, CD4⁺ 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.2024-01-01T00:00:00Z2024 Dec2026-06-05T20:40:25.927Z2026-05-21T03:13:02.909ZS-EPMC116250053926587710.1016/j.jaci.2024.08.026