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Characterization and biological significance of IL-23-induced neutrophil polarization

Abstract

Neutrophils are heterogeneous with distinct subsets, and can switch phenotypes to exert regulatory functions on immunity. We herein demonstrate that IL-23-treated neutrophils selectively produce IL-17A, IL-17F and IL-22, and display a distinct gene expression profile in contrast to resting and lipopolysaccharide-treated neutrophils. IL-17+ neutrophils are present in the colons of mice with dextran sulfate sodium-induced colitis. Adoptive transfer of IL-23-treated neutrophils significantly promotes pathogenesis in this model. IL-23 induces neutrophil polarization through STAT3-dependent RORĪ³t and BATF pathways. Thus, IL-23-induced neutrophil polarization expresses a unique cytokine-producing profile, which may contribute to IL-23-mediated inflammatory diseases.

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Acknowledgements

We thank Dr Aqeel Javeed for his kind review of the manuscript. This work was supported by grants from the National Basic Research Program of China (2014ZX10002002-001-002, YZ; 2011CB710903, YZ), the National Natural Science Foundation of China for General and Key Programs (81530049, 81130055, YZ), the Knowledge Innovation Program of the Chinese Academy of Sciences (XDA04020202-19, YZ), the Beijing Municipal Hospital Authority ā€˜Yangfan Programā€™ (ZYLX201408, XZ), and the CAS/SAFEA International Partnership Program for Creative Research Teams (YZ).

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YL, LZ, ZC and TY designed and carried out the experiments, analyzed the data and wrote the manuscript; H-XS analyzed the microarray data; FY, WW and YH performed the animal model experiments and real-time PCR assays; PW performed the ELISA assays; QZ and YT performed the flow cytometry; LZ, XZ and YZ designed the experiments, analyzed the data, wrote the manuscript and provided overall supervision.

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Correspondence to Lianfeng Zhang, Xiaodong Zhang or Yong Zhao.

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Li, Y., Zhu, L., Chu, Z. et al. Characterization and biological significance of IL-23-induced neutrophil polarization. Cell Mol Immunol 15, 518ā€“530 (2018). https://doi.org/10.1038/cmi.2017.39

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