The early neutrophil-committed progenitors aberrantly differentiate into immunoregulatory monocytes during emergency myelopoiesis
The early neutrophil-committed progenitors aberrantly differentiate into immunoregulatory monocytes during emergency myelopoiesis
复制标题
DOI：
10.1016/j.celrep.2023.112165
复制
发表时间：
2023-02-28
期刊：
影响因子：
8.8
通讯作者：
Asano, Kenichi
中科院分区：
文献类型：
--
作者：
Ikeda, Naoki;Kubota, Hiroaki;Asano, Kenichi
炎症刺激引起紧急骨髓生成状态，导致嗜中性粒细胞样单核细胞扩增。然而，它们的功能，承诺的前体，或生长因子仍然难以捉摸。在这项研究中，我们发现，Ym1 + Ly6Chi单核细胞，嗜中性粒细胞样单核细胞的免疫调节实体，产生于嗜中性粒细胞1（proNeu1）的祖细胞。粒细胞集落刺激因子（G-CSF）通过以前未知的CD81 + CX3CR1lo单核细胞前体促进嗜中性粒细胞样单核细胞的产生。GFI 1促进proNeu2从proNeu1分化，但以产生嗜中性粒细胞样单核细胞为代价。在CD14 + CD16-单核细胞部分中发现了也响应于G-CSF而扩增的嗜中性粒细胞样单核细胞的人类对应物。通过CXCR1表达和抑制T细胞增殖的能力将人嗜中性粒细胞样单核细胞与CD14 + CD16-经典单核细胞区分开来。总之，我们的研究结果表明，嗜中性粒细胞样单核细胞在炎症条件下的异常扩增是小鼠和人类之间保守的过程，这可能有利于炎症的消退。
Inflammatory stimuli cause a state of emergency myelopoiesis leading to neutrophil-like monocyte expan-sion. However, their function, the committed precursors, or growth factors remain elusive. In this study we find that Ym1+Ly6Chi monocytes, an immunoregulatory entity of neutrophil-like monocytes, arise from pro-genitors of neutrophil 1 (proNeu1). Granulocyte-colony stimulating factor (G-CSF) favors the production of neutrophil-like monocytes through previously unknown CD81+CX3CR1lo monocyte precursors. GFI1 pro-motes the differentiation of proNeu2 from proNeu1 at the cost of producing neutrophil-like monocytes. The human counterpart of neutrophil-like monocytes that also expands in response to G-CSF is found in CD14+CD16- monocyte fraction. The human 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 inflamma-tory conditions is a process conserved between mouse and human, which may be beneficial for the resolu-tion of inflammation.