Mechanisms of tissue repair by immnuoregulatory monocytes

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03473
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• 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)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 単球 / 制御性 / マクロファージ / 組織障害 / 修復

Outline of Final Research Achievements

We previously identified a unique subset of monocytes, namely the immunoregulatory monocytes. These monocytes are produced during emergency myelopoiesis and are responsible for regulation of inflammation and tissue repair. The aim of this study is to elucidate the molecular mechanisms for differentiation and function of immunoregulatory monocytes. As results, we found that the immunoregulatory monocytes are differentiated in bone marrow through GMP-ProNeu1-GMP-MoP pathway, while conventional monocytes are differentiated through MDP-cMoP pathway. We also found that Irf8 and Gfi1 are involved in the regulation of immunoregulatory monocyte differentiation. In vivo and In vitro studies revealed that Granulocyte-colony stimulating factor (G-CSF) stimulates not only differentiation of neutrophils, but also immunoregulatory monocyte production.

Free Research Field

ライフサイエンス／免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究は、我々が世界に先駆けて同定した制御性単球の分化と役割を明らかにすることにより、現在の免疫学の中心課題の１つである単球およびマクロファージの形質転換の機構の全容解明を目指したものである。本研究成果は、緊急造血時におけるマクロファージの形質転換あるいは可塑性のメカニズムを理解する上でブレークスルーとなることが期待できるとともに、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。