Abstract
Eosinophils accumulate in different tissues in allergies, cancer, and infectious diseases, adopting distinct properties. Herein, we profiled murine esophageal eosinophils during allergic inflammation using single-cell sequencing, epigenomic mapping, and flow cytometry. Esophageal eosinophils displayed an altered chromatin accessibility profile compared to bone marrow eosinophils, with 761 epi-transcriptionally regulated genes enriched in inflammation, immunoregulation, bacterial sensing, angiogenesis, migration, and apoptosis. The local environment entrains the unique esophageal eosinophil immunophenotype, as suggested by eosinophil-esophageal epithelial co-cultures, esophageal eosinophil transcriptional similarities regardless of the upstream cytokines driving their esophageal localization, and transcription factor gene editing altering esophageal eosinophilia and the associated eosinophil and global esophageal transcriptomes. Finally, the epigenomic and transcriptomic properties of murine esophageal eosinophils are largely conserved in humans. Thus, our data indicate that tissue specialization of esophageal eosinophils is entrained by local environmental cues that induce genome-wide epigenetic reprogramming and regulated by discrete transcription factors and provide a public, epigenetic database of murine tissue eosinophils.