Regulation of lipid-reactive lymphocytes for IBD treatment

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09372
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• 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) ; 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): 2017-04-01 – 2020-03-31
• Keywords: 免疫 / 腸管免疫 / 消化器病学 / 炎症性腸疾患

Outline of Final Research Achievements

Inflammatory bowel disease (IBD) 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 lipid-reactive lymphocyte populations, such as natural killer T cells, in IBD pathology. In this regards, we were able to observe ex vivo activities where proliferation of these lymphocytes can be modulated by intestinal epithelial cells derived from mouse tissues. Defining the physiological mechanisms of intestinal epithelial cells will lead to a significant understanding of the manner in which manipulation of lipid-reactive lymphocyte function may provide insights into novel therapeutic methods for the treatment of IBD.

Free Research Field

医歯薬学（内科系臨床医学）

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であることにある。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「脂質に対する粘膜免疫応答」の機能解析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細胞治療、分子治療開発へ向けた理論、技術基盤の創出に発展するものと期待できる。