Vitamin A regulates autophagy of intestinal macrophages

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09366
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hirosaki University
• Principal Investigator: Hiraga Hiroto 弘前大学, 医学研究科, 助教 (80637546)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ビタミンA / マクロファージ / オートファジー

Outline of Final Research Achievements

1. IL-1b production and non-canonical inflammasome activity of lamina propria separated by EDTA perfusion method were significantly higher in VAD mice compared with VAS mice, whereas TNF-a production was not increased. 2. Pyroptosis through non-canonical inflammasome signaling was increased in RAW264.7 cells pre-treated with Ro41-5253. 3. VAD mice treated with anti-IL-1b monoclonal antibody revealed amelioration of DSS-induced colitis in both of survival rate and bodyweight course. 4. serum vitamin A levels of active CD patients are lower than those of inactive CD patients, and serum vitamin A levels are related with disease activity and CRP.

Free Research Field

消化管免疫

Academic Significance and Societal Importance of the Research Achievements

VADマウスでは腸炎モデル・感染モデルのいずれにおいても宿主抵抗性が減弱しており、ビタミンAがマクロファージのパイロトーシスに及ぼす影響と炎症性腸疾患の病因・病態に関与している可能性が示唆された。ビタミンAが自然免疫系におけるパイロトーシスに及ぼす影響を明らかにすることで、自己炎症性疾患に対する寛解導入・維持療法への応用や診断・治療効果判定の新規バイオマーカーとなる可能性があるという点で非常に有意義と考えられた。