Elucidation of redox control in inflammasome activation by suspended particulate matter

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06848
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 45060:Applied anthropology-related
• Research Institution: Kobe Gakuin University
• Principal Investigator: Onodera Akira 神戸学院大学, 薬学部, 助教 (40598380)
• Co-Investigator(Kenkyū-buntansha): 河合 裕一 神戸学院大学, 薬学部, 名誉教授 (00102921) ; 角田 慎一 神戸学院大学, 薬学部, 教授 (90357533)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: PM2.5 / インターフェロン

Outline of Final Research Achievements

Suspended particulate matter (SPM) in the air is a matter of great concern as it is associated with various disease incidences/exacerbations. This study focused on the intracellular and in vivo SPM accumulation in the lysosomes of human airway epithelial cells and dendritic cells to understand its role in the deterioration of lysosomal pH homeostasis and inhibition of interferon production via Toll-like receptors localized in the lysosomes. Additionally, animal experiments showed that subcutaneous SPM administration transported it to the lymph node, and it was associated with continuous accumulation in the lymph node even after 6 months. The above finding indicates that SPM inhibits the function of lysosomes and lymph nodes, which are the cornerstones of immunity, suggesting a relationship between SPM and a weak immune system.

Free Research Field

免疫毒性学

Academic Significance and Societal Importance of the Research Achievements

生体内に取込まれる大気中の浮遊粒子状物質（SPM）は、免疫の力で対処する必要があり、どのような影響の原因となるかの分子機序の解明が求められる。本研究では、これまで明らかでない蓄積性と免疫力との関連を見出し、さらにリソソームがその中心となることを明らかとした。近年、リソソームの恒常性の維持がCOVID-19を含めた複数の疾患治療の標的として注目されており、本研究成果はこれら創薬開発の一助となるものと考えられる。