Development of new therapy for eosinophilic gastrointestinal diseases targeting the regulation of mucosal barrier

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08480
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Hyogo Medical University
• Principal Investigator: Oshima Tadayuki 兵庫医科大学, 医学部, 准教授 (00381814)
• Co-Investigator(Kenkyū-buntansha): 福井 広一 兵庫医科大学, 医学部, 准教授 (60378742) ; 三輪 洋人 兵庫医科大学, 医学部, 教授 (80190833)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 好酸球性消化管疾患 / 細胞間接着装置 / タイト結合 / クローディン

Outline of Final Research Achievements

Esophageal epithelial barrier function, and mast cell infiltration, as well as chemokine levels in eosinophilic esophagitis (EoE) patients before and after treatment were evaluate. Esophageal Epithelial infiltration of mast cells, and permeability were increased in EoE patients. Levels of IL-13, calpain-14, and eotaxin-3 mRNAs were upregulated, while filaggrin, SPINK7, and involucrin mRNAs were downregulated in EoE patients. In patients achieving histologic remission diagnosed by eosinophil counts, a subset of EoE patients with unchanged permeability after treatment showed increased mast cell infiltration, IL-13, calpain-14, filaggrin and SPINK7 with decreased eotaxin-3 and involucrin. Other EoE patients with decreased permeability displayed decreased eotaxin-3, and mast cell infiltration, and increased, filaggrin, and SPINK7. Increased permeability of the esophagus in EoE patients without eosinophil infiltration after treatment was associated with mast cell infiltration.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

好酸球性食道炎は希少疾患であるが，最近日本においても増加傾向にあり，その病態は不明な点が多い．完全に食道の炎症が改善していない状況で治療を中断すると再度炎症が発生して症状に悩まされることになる．これまで食道粘膜内の好酸球浸潤が改善することで治癒判定がなされているが，好酸球浸潤が改善したあとも食道粘膜の透過性が上昇し，肥満細胞浸潤が見られることが明らかとなり，今後治療の判定方法を再考する必要がある．