Gut homeostasis regulated by epithelia-immune cell interaction

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07184
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Toho University
• Principal Investigator: Naito Taku 東邦大学, 医学部, 准教授 (10568728)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: T細胞 / エピジェネティクス / 腸上皮間リンパ球

Outline of Final Research Achievements

The role of Eed, a mediator of repressive histone modification, in differentiation and maintenance of intraepithelial lymphocytes (IELs) was examined. Loss of Eed in mouse resulted in the trend of increased CD4+ CD8+ IEL. In vitro culture system identified a cell adhesion molecule as an enhancing factor of CD4+ CD8+ IEL differentiation， which was further enhanced by Eed heterozygous deletion. In addition, loss of Eed affected differentiation/survival of CD4+ but not much of CD8+ IELs. These results suggested that the interaction between cell adhesion molecule and epigenetic machinery plays a role in the gut homeostasis.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

腸管は無害・有害を問わず恒常的に異物にさらされており、その恒常性の維持は個体の生存にとって重要である。腸管恒常性維持を担う分子機構の解明は、炎症性腸疾患（IBD）の新規治療作用点の同定につながることが期待される。本研究では従来からIBDの治療標的となってきた細胞接着分子がエピジェネティックな分子機構を介して腸管恒常性維持を制御していることを示唆しており、IBDの新たな治療標的候補としての抑制的ヒストン修飾の可能性を示した。