The early neutrophil-committed progenitors aberrantly differentiate into immunoregulatory monocytes during emergency myelopoiesis

• Published in: Cell reports (Cambridge) Vol. 42; no. 3; p. 112165
• Main Authors: Ikeda, Naoki, Kubota, Hiroaki, Suzuki, Risa, Morita, Mitsuki, Yoshimura, Ayana, Osada, Yuya, Kishida, Keigo, Kitamura, Daiki, Iwata, Ayaka, Yotsumoto, Satoshi, Kurotaki, Daisuke, Nishimura, Koutarou, Nishiyama, Akira, Tamura, Tomohiko, Kamatani, Takashi, Tsunoda, Tatsuhiko, Murakawa, Miyako, Asahina, Yasuhiro, Hayashi, Yoshihiro, Harada, Hironori, Harada, Yuka, Yokota, Asumi, Hirai, Hideyo, Seki, Takao, Kuwahara, Makoto, Yamashita, Masakatsu, Shichino, Shigeyuki, Tanaka, Masato, Asano, Kenichi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.03.2023; Elsevier
• Subjects: Animals; Cell Differentiation; CP: Immunology; CXCR1; demand-adapted myelopoiesis; emergency myelopoiesis; G-CSF; Granulocyte Colony-Stimulating Factor; Humans; machine learning; Mice; monocyte; Monocytes - physiology; Myelopoiesis; neutrophil-like monocyte; Neutrophils; ontogeny; Ym1; demand-adapted myelopoiesis; CP: Immunology; emergency myelopoiesis; CXCR1; monocyte; neutrophil-like monocyte; Ym1; machine learning; G-CSF; ontogeny
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112165

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 Ym1+Ly6Chi monocytes, an immunoregulatory entity of 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. GFI1 promotes 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 inflammatory conditions is a process conserved between mouse and human, which may be beneficial for the resolution of inflammation. [Display omitted] •Mouse neutrophil-like monocytes arise from proNeu1 during emergency myelopoiesis•G-CSF favors a differentiation of proNeu1 into CD81+CX3CR1lo monocyte precursors•Human CXCR1+CD14+CD16− monocytes also expand in response to G-CSF treatment•Human neutrophil-like monocytes suppress the proliferation of T cells Ikeda et al. find that immunoregulatory monocytes expand in response to G-CSF during emergency myelopoiesis. Unlike classical monocytes that differentiate from monocyte-dendritic cell progenitors through the common monocyte progenitors, immunoregulatory monocytes differentiate from early neutrophil progenitors. These findings may be applied to the development of immunoregulatory monocyte-targeted therapy for human inflammatory diseases.