Intraesophageal administration of oxazolone to skin-sensitized mice results in experimental eosinophilic esophagitis resembling human disease

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease triggered by food and/or environmental allergens. While much data has accumulated on the epithelial component of EoE pathogenesis, less is known regarding the contribution of additional components to the development of EoE, in part due to the lack of a robust and reproducible mouse model, which mimics human disease. Mice were skin-sensitized using 4-ethoxymethylene-2-phenyl-2-oxazolin (OXA, 1%). After seven days, mice were skin-challenged (0.5% OXA, 5 times) and levels of serum IgE determined (ELISA). Thereafter, the mice were treated intra-esophageally (1% OXA, 8 times) and twenty-four hours after last treatment, the mice were euthanized. Subsequently, the esophagus was obtained, fixed and slides were stained (H&E, chloroacetate esterase, anti-EPX, anti-Ki-67). RNA was extracted and sequenced for transcriptome analysis and compared with human EoE RNAseq data OXA-treated mice displayed elevated IgE and exhibited gross dysphagia and weight loss. Histologically, OXA-treatment resulted in elevated eosinophilia, basal cell proliferation, and thickening of the lamina propria, which correlated with esophageal eosinophil counts. RNAseq of esophageal samples revealed increased expression of hallmark type 2-associated transcripts and displayed significant overlap with the human EoE transcriptome (384 upregulated transcripts, which represent ∼25% of the human EoE transcriptome). Bioinformatics analysis of the mutually upregulated transcripts revealed three distinct clusters associated with immune response, cell division, and epidermal development. We established a robust experimental model for EoE, resembling human disease. This model can serve to dissect molecular pathways in EoE and used for preclinical drug development.