Analysis of mesenchymal network for the mucosal healing

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H06243
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: Yosuke Kurashima 東京大学, 医科学研究所, 特任准教授 (30729372)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 炎症性腸疾患 / 間葉系細胞 / 粘膜修復 / 細胞外マトリックス / 創傷治癒

Outline of Final Research Achievements

Control of inflammatory responses as well as promotion of mucosal repair are required for the adequate treatment and cure of intestinal bowel diseases, such as Crohn's diseases and Ulcerative colitis. Mucosal mesenchymal cell populations function as a central source of extra cellular matrix and are required for the development and maintenance of stem cell niches in the colon. However, the precise mechanisms and subsets within the mucosal mesenchymal cells, involved in the process of mucosal repair, have not been well elucidated.
In this project, we first comprehensively analyzed the functional characteristics of those mesenchymal cells and found the unique and novel subsets are increased upon inflammatory responses. We further regulated the mesenchymal cellular population and found the disruption of its function resulted in the delay of mucosal repair. These results indicated the novel target of mesenchymal cells for promotion of mucosal repair was elucidated.

Free Research Field

粘膜免疫学

Academic Significance and Societal Importance of the Research Achievements

炎症性腸疾患をはじめとした慢性疾患の治療では、炎症反応の抑制のみならず、組織環境の適正化を導くことが重要である。組織微小環境を構築する細胞群として、線維芽細胞や筋線維芽細胞等の間葉系細胞が知られている。しかしながら、これらの詳細な解析が慢性炎症の新規治療法の確立に大きく貢献することは予想されつつも、その機能的制御法や組織修復に特化した細胞亜群については未だ不明な点が多く残されていた。
今後は、本研究によって明らかになった腸炎特異的に産生される粘膜修復因子や新規間葉系細胞亜群ならびに、そこから見出された新たな修復機序に立脚した、炎症性腸疾患の新たな治療戦略の確立が期待できる。