Vitamin A regulates autophagy of intestinal macrophages

Research Project

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
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	ビタミンA / マクロファージ / オートファジー / インフラマソーム
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.
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。