Immune regulation via intestinal autophagy for the treatment of Crohn's disease

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08438
• 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: Tokyo Medical and Dental University
• Principal Investigator: Nagahori Masakazu 東京医科歯科大学, 東京医科歯科大学病院, 准教授 (60420254)
• Co-Investigator(Kenkyū-buntansha): 永石 宇司 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (60447464) ; 渡辺 守 東京医科歯科大学, 高等研究院, 特別栄誉教授 (10175127)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 腸管免疫 / 腸管上皮 / 炎症性腸疾患

Outline of Final Research Achievements

Inflammatory bowel disease (IBD) including Crohn’s disease is characterized by unrestrained lymphocyte activation that results in the production of a variety of pro-inflammatory cytokines as well as other mediators. Understanding the mechanisms of lymphocyte regulation is therefore of significant importance in the study of dysregulated mucosal inflammation such as IBD. Associated with this, several studies have revealed the importance of autophagy in several cell types of IBD pathology, such as intestinal epithelial cells. In this regard, we were able to observe ex vivo activities where functions of these lymphocytes can be modulated by autophagy in the epithelial cells derived from mouse intestines. Defining the physiological mechanisms of autophagy in intestinal epithelial cells will lead to a greater understanding of how manipulation of effecter lymphocyte function may provide insights into novel treatment of IBD.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

炎症性腸疾患(IBD)の新規治療法開発を困難にしている理由は、腸管の免疫調節機構が未だ不明確なことにある。本研究の意義は腸管の粘膜免疫応答に関する研究を独自に展開してきた申請者らが、マウス腸管組織由来の上皮細胞初代培養技術を応用しつつ腸管特有の免疫調節機構を繙くことで、これまで実現し得なかった「腸管上皮細胞オートファジーによる免疫応答調節機構」の解明に向けた技術基盤を樹立するという免疫学的貢献ばかりでなく、IBDにおける腸管粘膜傷害に対するその特異的な免疫調節異常を標的とした新規治療法の開発基盤の創出に発展するものと期待できる。