NK cell-mediated immune regulation for IBD treatment

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08304
• 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: Fujii Toshimitsu 東京医科歯科大学, 医学部附属病院, 助教 (30547451)
• 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)
• 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, is characterized by unrestrained effecter T cell 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 critical in the study of dysregulated mucosal inflammation such as IBD. Associated with this, several studies have revealed the importance of natural killer (NK) cells in the pathogenesis of several autoimmune diseases. In this regard, we were able to observe ex vivo and in vivo activities of effecter T cells modulated by a subset of NK cells. Defining the physiological mechanisms of cytotoxicity by NK cells will lead to a greater understanding of how manipulating 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、NK細胞サブセットの免疫学的機能解析法、および培養技術をといった、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、これまで理解されていなかった「NK細胞サブセットによるエフェクターT細胞の抑制機能」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。