Elucidation of pediatric IBD control mechanism by Keap1-Nrf2 system and innate lymphoid cells and development to treatment

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17348
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center
• Principal Investigator: Nagashima Ryuichi 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん先進治療開発研究部, 研究技師 (20783707)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: ILC3 / IBD / Nrf2

Outline of Final Research Achievements

Since the innate immune system is deeply involved in the onset of inflammatory bowel disease (IBD), I analyzed the involvement of the Keap1-Nrf2 pathway in the oxidative stress response system in type 3 innate lymphoid cells (ILC3). In the DSS colitis model, NKp46-expressing ILC3 derived from the lamina propria was significantly increased in Nrf2-deficient mice, and IL-22 productive capacity was also high compared with WT mice. It was suggested that administration of Nrf2 activator reversed the series of reductions observed in Nrf2-deficient mice and contributed to the improvement of colitis. This study suggests that ILC3 plays an important role in colitis control and that they may be regulated by the Keap1-Nrf2 pathway of the oxidative stress response system.

Free Research Field

慢性炎症

Academic Significance and Societal Importance of the Research Achievements

本研究は、小児期に克服すべき炎症性腸疾患(IBD)の病態解明を目指し、比較的安全性の高いNrf2活性化剤を使用することで、腸炎に関与する新規リンパ球であるILC3の側面からIBDを捉えることに着目した。また、ILC3とKeap1-Nrf2経路の関連性は明らかになっておらず、本研究はその新しい制御機構の解析に迫った点で学術的意義は高い。小児期にIBDを克服することは、その後の社会生活への影響も抑えることができ社会的意義も高いと考えられる。