Effect of IFN-a and IFN-? on gene expression of 3D organoids derived from telomerase-immortalized normal human esophageal keratinocyte cell line, EPC2-hTERT.
Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophageal mucosa. While type 2 cytokines are predominant, targeting type 2 inflammation alone is not always effective for all patients. In EoE patients, the transcriptional profiling of  esophageal biopsy reveal upregulation of type I and II interferon (IFN) response, dysregulated immune signaling and downregulation of esophageal-specific genes in EoE patients. However, the role of interferon signaling during EoE is not fully understood. This study aims to investigate the impact of IFN signaling on esophageal epithelium and elucidate its role in EoE. IFN-? stimulation of esophageal epithelial cells triggered disruption of tissue differentiation, epithelial barrier integrity and cytotoxicity, which are relevant features of EoE immunopathology. Beyond EoE, our findings offer insights into esophageal disorders which may involve increased IFN-? signaling, including infections, gastrophageal reflux disease, and Barrett's esophagus. Overall design: Comparative transcriptomic profiling of 3D organoids derived from telomerase-immortalized normal human esophageal keratinocyte cell line, EPC2-hTERT