Single-Cell RNA Sequencing Identifies Metabolic Characteristics of T Cells in Eosinophilic Esophagitis
Oral Presentation and Poster, Gordon Conference on Food Allergy, Ventura, California
Eosinophilic esophagitis (EoE) is a tissue-specific allergic disorder characterized by the recruitment of eosinophils to the esophagus of affected patients. Treatment of EoE relies on antigen avoidance through the use of elimination diets, as the mechanisms of disease are not fully understood and interventional treatments are often ineffective. To understand the tissue ecosystem present in EoE, we used single-cell RNA sequencing to profile 24,968 single cells from biopsies of the esophagus and duodenum of nine patients with active EoE or with EoE in remission achieved by antigen avoidance. Analysis of the T cells recovered from these patients revealed T cell populations including CD4+ T helper cells, FOXP3+ T regulatory cells, CD8+ tissue resident memory cells, and GATA3+ effector-like Th2 cells. Th2 cells were enriched in the esophageal tissue of patients with active disease, expressed common mediators of Th2 including IL13 and IL5 as well as markers of pathogenic Th2 cells such as IL1RL1 and IL17RB. Paired alpha/beta TCR sequencing revealed that this population exhibited clonal expansion and contained an exclusive set of clones not detected in other T cell populations. Pathway analysis of the Th2 subset revealed an upregulation of genes associated with arachidonic acid metabolism and prostaglandin D2 (PGD2) synthesis, suggesting that pathogenic T cells contribute to the production of PGD2 in EoE, promote the recruitment of eosinophils. Thus, we identified a pathway upregulated in a clonal population associated with EoE, providing insight into the mechanisms of EoE and informing future interventional treatments.