Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio, USA.
Department of Pediatrics, CCHMC and the University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
JCI Insight. 2022 Jun 8;7(11):e159093. doi: 10.1172/jci.insight.159093.
Inflammation of the esophageal epithelium is a hallmark of eosinophilic esophagitis (EoE), an emerging chronic allergic disease. Herein, we probed human esophageal epithelial cells at single-cell resolution during homeostasis and EoE. During allergic inflammation, the epithelial differentiation program was blocked, leading to loss of KRT6hi differentiated populations and expansion of TOP2hi proliferating, DSPhi transitioning, and SERPINB3hi transitioning populations; however, there was stability of the stem cell-enriched PDPNhi basal epithelial compartment. This differentiation program blockade was associated with dysregulation of transcription factors, including nuclear receptor signalers, in the most differentiated epithelial cells and altered NOTCH-related cell-to-cell communication. Each epithelial population expressed genes with allergic disease risk variants, supporting their functional interplay. The esophageal epithelium differed notably between EoE in histologic remission and controls, indicating that remission is a transitory state poised to relapse. Collectively, our data uncover the dynamic nature of the inflamed human esophageal epithelium and provide a framework to better understand esophageal health and disease.
食管上皮炎症是嗜酸性食管炎 (EoE) 的标志，EoE 是一种新兴的慢性过敏性疾病。在此，我们在单细胞分辨率水平上探究了人类食管上皮细胞在稳态和 EoE 期间的状态。在过敏炎症期间，上皮分化程序被阻断，导致 KRT6hi 分化群体的丧失和 TOP2hi 增殖、DSPhi 过渡和 SERPINB3hi 过渡群体的扩张；然而，富含干细胞的 PDPNhi 基底上皮区室保持稳定。这种分化程序的阻断与转录因子的失调有关，包括最分化的上皮细胞中的核受体信号分子，以及改变的 NOTCH 相关细胞间通讯。每个上皮群体都表达了具有过敏疾病风险变异的基因，支持它们的功能相互作用。EoE 在组织学缓解和对照组之间的食管上皮存在显著差异，表明缓解是一种易于复发的短暂状态。总的来说，我们的数据揭示了人类受炎症影响的食管上皮的动态性质，并为更好地理解食管健康和疾病提供了一个框架。
