Antigen processing in intestinal epithelial cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05286
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• 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): 中村 哲也 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座教授 (70265809) ; 渡辺 守 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (10175127)
• Research Collaborator: ONIZAWA Michio ; SUZUKI Masahiro ; WATABE Taro ; TSUGAWA Naoya ; YAMADA Daiki ; KOJIMA Yudai
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 炎症性腸疾患 / 粘膜免疫 / 抗原提示

Outline of Final Research Achievements

IBD 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 regulation is therefore of significant importance to dysregulated mucosal inflammation such as IBD. Genome-wide association studies in the analysis of IBD have identified genetic risk foci. Several studies have especially revealed the important roles of antigen presentation-related genes in IBD, including the major histocompatibility complex class I and II. In this regards, we have observed that the expressions of these molecules in several cell types such as hematopoietic cells and epithelial cells were modulated by the up-regulated pro-inflammatory cytokines in vivo. Defining the mechanisms of antigen presentation will lead to a significant understanding of the manner in which manipulation of this 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

腸管の免疫調節機構が未だ不明確であることは、炎症性腸疾患(IBD)治療法開発を困難にしている。本研究の特徴は腸管免疫調節機構に関する研究を展開してきた申請者らが、正常腸上皮細胞の初代培養技術を応用したことで、IBDの病態理解に留まらず、これまで実現し得なかった「生理的粘膜免疫応答」の機能解析に向けた技術基盤樹立という免疫学的インパクト、さらには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。