Regulation of intestinal environment by Paneth cells and new therapeutic strategy for inflammatory bowel disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02788
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Hokkaido University
• Principal Investigator: Ayabe Tokiyoshi 北海道大学, 先端生命科学研究院, 教授 (90301019)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 炎症性腸疾患 / Paneth細胞 / 自然免疫 / 腸内細菌 / αディフェンシン / 腸内環境 / クローン病 / 小胞体ストレス

Outline of Final Research Achievements

Focusing on the regulation of the intestinal microbiota by antimicrobial peptide alpha-defensin secreted by Paneth cells in the small intestine, secretory responses of Paneth cells were visualized and revealed the site-selective granule secretory stimulation, i.e., lumen side or basal side, and the granule replenishment after secretion. This study clarified for the first time the correlation between abnormalities in quality and quantity of alpha-defensin and disruption of the intestinal microbiota, dysbiosis, associated with disease progression in Crohn's disease model mice, and further presented novel therapeutic strategy for inflammatory bowel disease in the light of regulating the intestinal environment.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

Paneth細胞の顆粒分泌評価系を確立し、コリン作動性刺激や細菌刺激でαディフェンシンを分泌することが示されて以来長年ディベートが続いていたPaneth細胞分泌応答の重要な課題を解決した学術的意義を有する。また、クローン病モデルマウスでPaneth細胞の過剰な小胞体ストレスがαディフェンシンの質的異常を生じ、還元型αディフェンシン分泌が腸内細菌叢破綻と腸炎進展を起こすことを示し、クローン病の病態理解と新規治療開発に新しい方向性を与えた学術的・社会的意義が大きい。