Study of tissue repair mechanisms targeting a novel monocyte subset

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15421
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Ikeda Naoki 東京薬科大学, 生命科学部, 嘱託助教 (90825473)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 好中球様単球 / 制御性単球 / 炎症抑制 / 組織修復 / Ym1 / CXCR1

Outline of Final Research Achievements

Inflammatory stimuli cause a state of emergency myelopoiesis leading to neutrophil-like monocyte expansion. However, their function, the committed precursors, or growth factors remain elusive. In this study we find that neutrophil-like monocytes arise from progenitors of neutrophil 1 (proNeu1). Granulocyte-colony stimulating factor (G-CSF) favors the production of neutrophil-like monocytes through previously unknown CD81+CX3CR1lo monocyte precursors. The human counterpart of neutrophil-like monocytes are discriminated from CD14+CD16－ classical monocytes by CXCR1 expression and the capacity to suppress T cell proliferation. Collectively, our findings suggest that the aberrant expansion of neutrophil-like monocytes under inflammatory conditions is a process conserved between mouse and human, which may be beneficial for the resolution of inflammation.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

感染や組織傷害により炎症が誘導されるが、その後の炎症収束機構は不明点が多く残されている。本研究により、好中球様単球を介した炎症抑制機構が明らかになり、炎症収束機構の一端が解明された。さらに、好中球様単球の分化機構も明らかになったことから、本研究成果が、同単球分化誘導による炎症抑制および組織修復促進を目的とした新規治療法開発に応用できる可能性がある。