Departments of Pediatrics, Children’s Medical Center, USA.
Am J Physiol Gastrointest Liver Physiol. 2012 Dec 1;303(11):G1175-87. doi: 10.1152/ajpgi.00313.2012. Epub 2012 Sep 27.
Eosinophilic esophagitis (EoE) is a recently recognized, immune-mediated disease characterized clinically by symptoms of esophageal dysfunction and histologically by eosinophil-predominant inflammation. The chronic esophageal eosinophilia of EoE is associated with tissue remodeling that includes epithelial hyperplasia, subepithelial fibrosis, and hypertrophy of esophageal smooth muscle. This remodeling causes the esophageal rings and strictures that frequently complicate EoE and underlies the mucosal fragility that predisposes to painful mucosal tears in the EoE esophagus. The pathogenesis of tissue remodeling in EoE is not completely understood, but emerging studies suggest that secretory products of eosinophils and mast cells, as well as cytokines produced by other inflammatory cells, epithelial cells, and stromal cells in the esophagus, all contribute to the process. Interleukin (IL)-4 and IL-13, Th2 cytokines overproduced in allergic disorders, have direct profibrotic and remodeling effects in EoE. The EoE esophagus exhibits increased expression of transforming growth factor (TGF)-β1, which is a potent activator of fibroblasts and a strong inducer of epithelial-mesenchymal transition. In addition, IL-4, IL-13, and TGF-β all have a role in regulating periostin, an extracellular matrix protein that might influence remodeling by acting as a ligand for integrins, by its effects on eosinophils or by activating fibrogenic genes in the esophagus. Presently, few treatments have been shown to affect the tissue remodeling that causes EoE complications. This report reviews the potential roles of fibroblasts, eosinophils, mast cells, and profibrotic cytokines in esophageal remodeling in EoE and identifies potential targets for future therapies that might prevent EoE complications.
嗜酸粒细胞性食管炎（EoE）是一种新近被认识的、由免疫介导的疾病，其临床特征为食管功能障碍，组织学表现为以嗜酸粒细胞浸润为主的炎症。EoE 的慢性食管嗜酸粒细胞浸润与组织重塑有关，包括上皮细胞增生、黏膜下纤维化和食管平滑肌肥大。这种重塑导致 EoE 常合并的食管环和狭窄，并使 EoE 食管容易发生黏膜脆性增加和疼痛性黏膜撕裂。EoE 组织重塑的发病机制尚未完全阐明，但新的研究表明，嗜酸粒细胞和肥大细胞的分泌产物，以及食管中其他炎症细胞、上皮细胞和基质细胞产生的细胞因子，都参与了这一过程。Th2 细胞因子白细胞介素（IL）-4 和 IL-13 在过敏疾病中过度产生，对 EoE 具有直接的促纤维化和重塑作用。EoE 食管表现出转化生长因子（TGF）-β1 的表达增加，TGF-β1 是成纤维细胞的有效激活剂，也是上皮-间充质转化的强烈诱导剂。此外，IL-4、IL-13 和 TGF-β 在调节外泌体蛋白periostin 方面都具有一定的作用，periostin 可以作为整合素的配体，通过影响嗜酸粒细胞或激活食管中的成纤维基因来影响重塑。目前，很少有治疗方法被证明能影响导致 EoE 并发症的组织重塑。本报告综述了成纤维细胞、嗜酸粒细胞、肥大细胞和成纤维化细胞因子在 EoE 食管重塑中的潜在作用，并确定了未来可能预防 EoE 并发症的治疗靶点。
