Transcriptomic profiling of esophageal epithelium reveals enrichment of IFN-? response gene signature during active EoE.

Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophageal mucosa. Although 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 reveals upregulation of type I and II interferon (IFN) response, dysregulated immune signaling, and downregulation of esophageal-specific genes. However, further investigation is needed to examine the gene expression changes in esophageal epithelium because it plays an important role in EoE. To investigate the upregulation of Interferon Stimulated Genes (ISGs) in EoE esophageal epithelium, we isolated epithelial cells from active EoE patients and non-EoE controls. We performed bulk RNA sequencing to analyze the epithelial-specific transcriptome in EoE. Unsupervised hierarchical clustering of the most variable genes differentiated the active EoE biopsies from non-EoE controls. Gene set enrichment analysis identified IFN-? response as the most significant upregulated pathway. Overall design: Comparative profiling of epithelial-specific transcriptome in EoE active and non-EoE controls.