Single cell RNA Squencing of Human Eosinophils in Allergc Inflammation in the Esophagus

Eosinophils are elusive cells involved in allergic inflammation. Herein, we profiled 586 human eosinophils from the circulation and an allergic inflammatory site, the esophagus, of patients with eosinophilic esophagitis by Seq-Well–based single-cell RNA sequencing. The esophageal eosinophils were composed of a population of activated eosinophils (enriched in 659 genes compared with peripheral blood-associated eosinophils) and a small population of eosinophils resembling peripheral blood eosinophils (enriched in 62 genes compared with esophageal eosinophils). Esophageal eosinophils expressed genes involved in sensing and responding to diverse stimuli, most notably interferon-Ɣ(IFN-Ɣ), interleukin 10 (IL-10), histamine and leukotrienes, and succinate metabolite signaling. Esophageal eosinophils were most distinguished from other esophageal populations by gene expression of the receptors CCR3, HRH4, SUCNR1, and VSTM1; transcription factors CEBPE, OLIG1, and OLIG2; protease PRSS33; and hallmark eosinophil gene CLC. A web of bidirectional eosinophil interactions with other myeloid cells, T cells, fibroblasts, and the epithelium and vasculature was derived. Comparing esophageal eosinophils and mast cells revealed that esophageal eosinophils expressed genes involved in DAP12 interactions, IgG receptor-triggered events, immunoregulation, and IL-10 signaling, whereas esophageal mast cells expressed genes involved in arachidonic acid metabolism and response to unfolded proteins. These findings indicate that esophageal eosinophils exist as two populations, a minority population resembling blood eosinophils and the other population characterized by high de novo transcription of diverse sensing receptors and inflammatory mediators readying them to intersect with diverse cell types.