International Session(Workshop)2(JSGE・JGES・JSGCS)
Fri. November 3rd   9:30 - 12:00   Room 9: Portopia Hotel Main Building Kairaku 3
Amphiregulin-producing Tpath2 cells have critical role in esophageal fibrosis of Eosinophilic Esophagitis
Tatsuya Kaneko1,2, Chiaki Iwamura2, Kiyoshi Hirahara2
1Department of Gastroenterology, Graduate School of Medicine, Chiba University, 2Department of Immunology, Graduate School of Medicine, Chiba University
Background: Eosinophilic esophagitis (EoE) is known as a disease that causes submucosal fibrosis and esophageal stricture with eosinophil infiltrations into the esophagus. However, pathogenesis of esophageal fibrosis has been unclear, and there is currently no established treatment to prevent or treat the fibrosis.
Objective: The purpose of this study was to elucidate cellular and molecular mechanisms of esophageal fibrosis.
Methods: We established a murine model of EoE accompanied with fibrosis by long-term intranasal administration of house dust mite antigen. Using this model mice, we examined pathogenic T helper 2 (Tpath2) cells in the esophagus by flow cytometric and histological analysis. We also analyzed biopsy samples of esophagus obtained from EoE patients using by single cell RNA sequencing, flowcytometry and immunohistochemistry.
Results: The number of amphiregulin- and IL-5-producing Tpath2 cells increased in the esophagus of the mouse model and localized in the fibrotic area. We also demonstrated that the amphiregulin production from Tpath2 cells was critical for the development of esophageal fibrosis. Analysis of human esophageal biopsy samples showed that amphiregulin-producing Tpath2 cells increased in EoE patients compared to control patients and associated with esophageal fibrosis.
Conclusion: Amphiregulin produced by Tpath2 cells is contributed to the esophageal fibrosis in EoE and can be therapeutic target.
Index Term 1: Eosinophilic Esophagitis
Index Term 2: Pathogenic T helper 2 cells
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