Eosinophilic esophagitis (EoE) is an allergic disorder characterized by the recruitment of eosinophils to the esophagus, resulting in chronic inflammation. We sought to understand the cellular populations present in tissue biopsies of patients with EoE and to determine how these populations are altered between active disease and remission. To this end, we analyzed cells obtained from esophageal biopsies, duodenal biopsies, and peripheral blood of patients with EoE diagnosed with active disease or remission with single-cell RNA and T cell receptor (TCR) sequencing. Pathogenic effector T_H2 (peT_H2) cells present in the esophageal biopsies of patients with active disease expressed distinct gene signatures associated with the synthesis of eicosanoids. The esophageal tissue–resident peT_H2 population also exhibited clonal expansion, suggesting antigen-specific activation. Peripheral CRTH2⁺CD161⁻ and CRTH2⁺CD161⁺ memory CD4⁺ T cells were enriched for either a conventional T_H2 phenotype or a peT_H2 phenotype, respectively. These cells also exhibited substantial clonal expansion and convergence of TCR sequences, suggesting that they are expanded in response to a defined set of antigens. The esophagus-homing receptor GPR15 was up-regulated by peripheral peT_H2 clonotypes that were also detected in the esophagus. Finally, GPR15⁺ peT_H2 cells were enriched among milk-reactive CD4⁺ T cells in patients with milk-triggered disease, suggesting that these cells are an expanded, food antigen–specific population with enhanced esophagus homing potential.

嗜酸性粒细胞性食管炎 (EoE) 是一种过敏性疾病，其特征是嗜酸性粒细胞聚集到食管，导致慢性炎症。我们试图了解 EoE 患者组织活检中存在的细胞群，并确定这些细胞群在疾病活动期和缓解期之间如何变化。为此，我们通过单细胞 RNA 和 T 细胞受体 (TCR) 测序分析了从诊断为活动性疾病或缓解期的 EoE 患者的食管活检、十二指肠活检和外周血中获得的细胞。活动性疾病患者食管活检中存在的致病效应 T _H 2 (peT _{H 2) 细胞表达与类二十烷酸合成相关的独特基因特征。}食管组织中的 peT _H 2 群体也表现出克隆扩张，表明抗原特异性激活。外周 CRTH2 ⁺ CD161 ^-和 CRTH2 ⁺ CD161 ⁺记忆 CD4 ⁺ T 细胞分别富集传统 T _H 2 表型或 peT _H 2 表型。这些细胞还表现出大量的克隆扩增和 TCR 序列的收敛，表明它们是响应一组确定的抗原而扩增的。食管归巢受体GPR15被外周 peT _H 2 克隆型上调，这些克隆型也在食管中检测到。最后，在患有牛奶引发疾病的患者中， GPR15 ⁺ peT _{H 2 细胞在牛奶反应性 CD4} ⁺ T 细胞中富集，表明这些细胞是一个扩展的食物抗原特异性群体，具有增强的食道归巢潜力。