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Publication : Neutrophils promote the development of reparative macrophages mediated by ROS to orchestrate liver repair.

First Author  Yang W Year  2019
Journal  Nat Commun Volume  10
Issue  1 Pages  1076
PubMed ID  30842418 Mgi Jnum  J:273885
Mgi Id  MGI:6287101 Doi  10.1038/s41467-019-09046-8
Citation  Yang W, et al. (2019) Neutrophils promote the development of reparative macrophages mediated by ROS to orchestrate liver repair. Nat Commun 10(1):1076
abstractText  Phagocytes, including neutrophils and macrophages, have been suggested to function in a cooperative way in the initial phase of inflammatory responses, but their interaction and integration in the resolution of inflammation and tissue repair remain unclear. Here we show that neutrophils have crucial functions in liver repair by promoting the phenotypic conversion of pro-inflammatory Ly6C(hi)CX3CR1(lo) monocytes/macrophages to pro-resolving Ly6C(lo)CX3CR1(hi) macrophages. Intriguingly, reactive oxygen species (ROS), expressed predominantly by neutrophils, are important mediators that trigger this phenotypic conversion to promote liver repair. Moreover, this conversion is prevented by the depletion of neutrophils via anti-Ly6G antibody, genetic deficiency of granulocyte colony-stimulating factor, or genetic deficiency of NADPH oxidase 2 (Nox2). By contrast, adoptive transfer of WT rather than Nox2(-/-) neutrophils rescues the impaired phenotypic conversion of macrophages in neutrophil-depleted mice. Our findings thus identify an intricate cooperation between neutrophils and macrophages that orchestrate resolution of inflammation and tissue repair.
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