Host-microbe interaction through innate immune factor DAO

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09327
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Keio University
• Principal Investigator: Sasabe Jumpei 慶應義塾大学, 医学部(信濃町), 講師 (10398612)
• Research Collaborator: SUZUKI Masataka
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: D-アミノ酸 / 共生細菌 / 小腸上皮 / 獲得免疫

Outline of Final Research Achievements

We investigated expressional regulation of the mucosal innate defense factor D-amino acid oxidase, DAO, and immune modulation by DAO in mammals. We have shown that DAO expression was induced by commensal microbiota through non-canonical pathway that does not involve canonical signaling molecules, MyD88 or RIPK2. We have also found that D-amino acid metabolism by DAO regulates adaptive immune system: (1) activation of immune responses through T-cell dependent signals triggered by DAO-sensitive microbiota, and (2) increase capacity of the responses through T-cell independent signals.

Free Research Field

腸内細菌

Academic Significance and Societal Importance of the Research Achievements

D-アミノ酸は共生細菌によって産生される代謝物で、我々の腸内でも多く産生されている。小腸DAOはD-アミノ酸制御を介して腸内細菌の制御に関与していることが知られており、本研究では宿主獲得免疫調節に関与することを明らかにした。DAOの制御機構も本研究で一部明らかにし、DAOの制御やD-アミノ酸調節が腸内細菌や免疫調節に将来的に利用できる可能性があることを示した。