MinYeong Lim, Taesoo Kim, Hyesung Kim, Bo Gun Jang, Jae Kyung Myung, Hye Young Kim
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引用次数: 0
Abstract
Eosinophilic esophagitis (EoE) is a chronic allergic disorder characterized by eosinophilia and epithelial thickening, resulting in dysphagia. While emerging evidence implicates increased frequencies of group 2 innate lymphoid cells (ILC2s) and increased interleukin (IL)-33 expression in EoE pathogenesis, the precise mechanisms remain unclear. In this study, we investigated the role of ILC2s in EoE pathogenesis. We observed an abundance of KLRG1+ ILC2s in the esophagi of healthy mice, with their numbers significantly increasing in murine EoE models and humans. Using a murine EoE model, we demonstrated the recapitulation of EoE-associated features, including basal-cell hyperproliferation, epithelial thickening, and eosinophilia. Notably, these characteristics are absent in ILC-deficient mice, whereas mice lacking IL-5 or eosinophils display epithelial defects, highlighting the pivotal role of ILC2s in EoE pathogenesis. Further investigations revealed increased amphiregulin (Areg) production by esophageal ILC2s in mice. The administration of Areg induced epithelial defects similar to those observed in EoE. Mechanistic studies using human esophageal cell lines revealed Areg-induced phosphorylation of epidermal growth factor receptor (EGFR). Significatntly, treatment with anti-Areg agents and EGFR inhibitors effectively attenuated EoE development, highlighting the therapeutic potential of targeting the Areg-EGFR axis.
期刊介绍:
Cellular & Molecular Immunology, a monthly journal from the Chinese Society of Immunology and the University of Science and Technology of China, serves as a comprehensive platform covering both basic immunology research and clinical applications. The journal publishes a variety of article types, including Articles, Review Articles, Mini Reviews, and Short Communications, focusing on diverse aspects of cellular and molecular immunology.