Mechanisms of phenotypic changes in macrophages during tissue injury

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04068
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: TANAKA MASATO 東京薬科大学, 生命科学部, 教授 (00294059)
• Co-Investigator(Kenkyū-buntansha): 大村谷 昌樹 兵庫医科大学, 医学部, 教授 (60398229)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: マクロファージ / 組織傷害 / 形質転換 / 単球

Outline of Final Research Achievements

Macrophages play diverse roles in tissue injury. However, it remains unknown how these macrophages change phenotype according to each phase of tissue injury. This research aimed to reveal mechanisms of phenotypic changes in macrophages during tissue injury. As a result, we demonstrated that two transcriptional factors, c-Maf and Nrf2, determine the phenotype of CD169 macrophages during tissue injury. Furthermore, we identified a novel subpopulation of Ly6C-positive monocytes (Ym1- positive monocytes) in mice. Ym1-positive monocytes are generated in bone marrow during the phase of tissue repair, and contribute to resolution of inflammation and tissue repair in damaged tissues.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

マクロファージは、組織傷害や炎症時に、外界の刺激や環境に素早く対応し、機能的、構造的な変化を起こすことが知られているが、その分子機構は不明な点が多かった。本研究の成果は、特定の転写因子がマクロファージの形質転換に分子スイッチとして働くことを明確に示しており、マクロファージの可塑性および組織傷害の病理を理解する上で有用な知見である。また、得られた知見は将来的に、炎症制御や組織修復促進を目的とした新たな疾患治療法の開発につながる可能性がある。