Involvement of dendritic cells autophagy in the pathogenesis of COPD

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09674
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Hashimoto Mitsuo 東京慈恵会医科大学, 医学部, 助教 (00771742)
• Co-Investigator(Kenkyū-buntansha): 荒屋 潤 東京慈恵会医科大学, 医学部, 教授 (90468679)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 樹状細胞

Outline of Final Research Achievements

Dendritic cells (DC) are though to be important for the introducing inflammatory cells and fibrotic changes in the lung of COPD patients. We aimed to elucidate that autophagy activity inside DC might control the migration of Th1, Th17 and neutrophils into the lung. By examining the lung sample of COPD patients, ubiquitin and p62 expressions inside DC are more pronounce in COPD patients than normal patients, suggesting attenuated activity of autophagy inside DC. In vitro experiment, DC were differentiated from bone marrow by GM-CSF, and Cigarette smoke extract stimulations made DCs from WT mouse to produce more cytokines than Parkin knockout mouse- derived BMDC when LPS was added.

Free Research Field

COPD

Academic Significance and Societal Importance of the Research Achievements

マウスの骨髄からGM-CSFでBMDCが誘導されることを確認した。このBMDCを使用した結果、サイトカインの分泌は、CSE刺激群でより多く出る傾向が見られたが、Parkinノックアウトマウスから誘導したDCからは、サイトカインは抑制される傾向が見られた。DC内のマイトファジーの低下がサイトカインの分泌抑制に関与している可能性が示唆された。