Cell Reports (Mar 2023)

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

  • Naoki Ikeda,
  • Hiroaki Kubota,
  • Risa Suzuki,
  • Mitsuki Morita,
  • Ayana Yoshimura,
  • Yuya Osada,
  • Keigo Kishida,
  • Daiki Kitamura,
  • Ayaka Iwata,
  • Satoshi Yotsumoto,
  • Daisuke Kurotaki,
  • Koutarou Nishimura,
  • Akira Nishiyama,
  • Tomohiko Tamura,
  • Takashi Kamatani,
  • Tatsuhiko Tsunoda,
  • Miyako Murakawa,
  • Yasuhiro Asahina,
  • Yoshihiro Hayashi,
  • Hironori Harada,
  • Yuka Harada,
  • Asumi Yokota,
  • Hideyo Hirai,
  • Takao Seki,
  • Makoto Kuwahara,
  • Masakatsu Yamashita,
  • Shigeyuki Shichino,
  • Masato Tanaka,
  • Kenichi Asano

Journal volume & issue
Vol. 42, no. 3
p. 112165

Abstract

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Summary: 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.

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