Establishment foundation of regulation against immunosenescence targeting myeloid-derived suppressor cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07345
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Tokyo University of Science, Yamaguchi
• Principal Investigator: Horie Ichiro 山陽小野田市立山口東京理科大学, 薬学部, 講師 (10609514)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 骨髄由来免疫抑制細胞 / 老化 / 免疫老化 / 細胞分化 / 慢性炎症

Outline of Final Research Achievements

To prevent age-related diseases increasing in super-aging society, it is necessary to control immunosenescence, which contributes to the onset of disease during the aging process, however, the complete mechanisms and target cells of immunosenescence have not been elucidated. Recently, it has been suggested the possibility that myeloid-derived suppressor cells (MDSC) may be involved in immunosenescence, in this study, I investigated the dynamics and the function of MDSC using aging-model mice (SOD1-KO mice). As a result of this study, I found that MDSC with high immunosuppressive ability increased in an age-dependent manner in SOD1-KO mice, and this increase happened prior to liver fibrosis and chronic inflammation, suggesting the importance of MDSC as target cells in regulating immunosenescence.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

MDSCは，従来がん免疫の回避に寄与することは示唆されていたものの，MDSCと老化の関連性は，老齢マウスでMDSCが増加するという情報のみで，動態や機能的変化の時系列やその役割は明確ではなかった．本研究によって，加齢性表現型の中でも，MDSCの増加が極めて早期に生じ，炎症や線維化に先行することが判明したことで，MDSCを標的とした抗老化戦略の有用性が明確となり，MDSCの分化・機能を調節するという新たな抗老化戦略を提唱し，その実効性を検証するための重要な基盤を構築することができたと考えられる．