Analysis of pathophysiology in the setting of IBD

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03658
• 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: Tokyo Medical and Dental University
• Principal Investigator: NAGAISHI Takashi 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)
• Co-Investigator(Kenkyū-buntansha): 長堀 正和 東京医科歯科大学, 東京医科歯科大学病院, 准教授 (60420254)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 免疫学 / 腸管免疫 / 消化器病学 / 炎症性腸疾患

Outline of Final Research Achievements

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is characterized by unrestrained lymphocyte activation that results in the production of a variety of pro-inflammatory cytokines and other mediators. Understanding the mechanisms of lymphocyte activation is critical in the study of dysregulated mucosal inflammation such as IBD. In this regard, we have recently established an intravital imaging system to investigate several murine models of IBD, such as DSS colitis and oxazolone colitis. Associated with this, we were able to observe in vivo activities where functions of effecter lymphocytes can be activated in several IBD models. Defining the physiological mechanisms of unrestrained lymphocyte activation will lead to a greater understanding of how manipulation of effecter lymphocyte function may provide insights into novel treatment of IBD.

Free Research Field

消化器内科学

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、ライブイメージング技術、FRET技術、および遺伝子導入系等といった、これまでの技術と知見を統合しつつ腸管特有の免疫調節機構を繙くことで、これまでベールに包まれていた「GALT内抗原提示細胞の新たな調節機構」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の発症時におけるその変調に対して極めて病態特異性の高い新規診断・治療法開発の理論基盤の創出に発展するものと期待できる。