Multi Regulatory System for Gut Homeostasis and Inflammation

2022 Fiscal Year Final Research Report

• Project/Area Number: 18H05280
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Review Section: Broad Section I
• Research Institution: Chiba University (2022); The University of Tokyo
• Principal Investigator: Hiroshi Kiyono 千葉大学, 未来医療教育研究機構, 卓越教授 (10271032)
• Co-Investigator(Kenkyū-buntansha): 倉島 洋介 千葉大学, 大学院医学研究院, 准教授 (30729372)
• Project Period (FY): 2018-06-11 – 2023-03-31
• Keywords: 炎症性腸疾患 / 臓器連関 / 上皮細胞 / 腸内細菌 / 慢性炎症 / 粘膜免疫 / パネート細胞 / 線維芽細胞

Outline of Final Research Achievements

Inflammatory bowel disease (IBD) and its complications are chronic and difficult　to treat. In addition, the complete mechanism underlying their pathogenesis is not fully understood. In this study, we aimed to elucidate the maintenance mechanism of intestinal mucosal homeostasis and establish new methods for disease control by investigating the multi regulatory system in the mucosal tissues. Through analysis of organ and cellular interactive connections both inside and outside the mucosal tissues, we discovered a new biological defense mechanism by which the pancreas protects the intestine from bacterial infections, identified a new subset of intestinal "Paneth cells" responsible for the producing antimicrobial peptides and their differentiation mechanism, and also identified a novel group of mesenchymal cells as therapeutic targets for IBD. These achievements are expected to serve as an applied foundation for the disease prevention and the development of new therapies.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究は、炎症性腸疾患の発症や重症化につながる組織恒常性の破綻について、粘膜免疫システムに留まることなく、それを取り巻く「腸管粘膜外支持組織」との相互作用による「階層的粘膜支持連関システム」という新しい視点からの生体高次複雑系の一翼を担う腸管監視・防御機構を明らかにした。炎症遷延化に関わる新たな治療標的細胞の同定のみならず、腸を保護する他の臓器の機能への介入による腸疾患制御法の開発につながる重要な成果が得られた。これらの研究成果は「階層的粘膜支持連関システム」を標的とした炎症性疾患ならびにその合併症に対する新たな画期的な予防・治療法の開発に繋がる可能性を有している。