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Characterization and allergic role of IL-33-induced neutrophil polarization

Cellular and Molecular Immunology | Download Citation

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Abstract

Neutrophils are involved in the pathogenesis of allergy. However, the contribution of the different functionally polarized neutrophils in allergy needs to be clarified. We sought to define the characteristics of interleukin (IL)-33-induced neutrophils and the involvement of this subset of polarized neutrophils in allergic pathogenesis. Freshly isolated neutrophils were treated with different cytokines and the cytokine expression levels were detected by real-time PCR. The gene expression profile of IL-33-induced neutrophils was determined by microarray assay. Adoptive transfer assay was used to investigate the function of IL-33-induced neutrophils in an ovalbumin (OVA)-induced allergic asthma model. IL-33-treated neutrophils selectively produced IL-4, IL-5, IL-9 and IL-13 (referred as to N(IL-33) cells) and displayed a distinctive gene expression profile in sharp contrast to resting and lipopolysaccharide (LPS)-treated neutrophils. IL-33-induced neutrophils expressed high Levels of IL-1R2 on cell surface, whereas resting and LPS-treated neutrophils did not, indicating IL-1R2 might be used as a biomarker for N(IL-33) cells. Importantly, N(IL-33) neutrophils exist in the lungs of OVA-induced allergic asthma mice. Adoptive transfer of N(IL-33) neutrophils significantly promotes the severity of the lung pathogenesis in this model. IL-33 induces neutrophil polarization through c-Jun N-terminal kinase- and nuclear factor-κB-dependent pathways. A previously unappreciated neutrophil polarization driven by IL-33 with unique cell surface markers and cytokine/chemokine-producing gene profile was defined. The newly identified N(IL-33) subpopulation may have significant contribution to IL-33-related pathogenesis.

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Acknowledgements

We thank Dr Lianjun Zhang and Dr Aqeel Javeed for their kind review of the manuscript. This work was supported by grants from the National Natural Science Foundation of China for General and Key Programs (81530049 and 81130055 to YZ), Knowledge Innovation Program of Chinese Academy of Sciences (XDA04020202-19 to YZ), the CAS/SAFEA International Partnership Program for Creative Research Teams (to YZ) and Beijing Municipal Hospital Authority ‘Yangfan Program’ (ZYLX201408 to XZ).

Author contributions

BS, LZ and YT designed and carried out the experiments, analyzed data and wrote the manuscript; H-XS analyzed microarray data; PW performed real-time PCR assays; YZ performed ELISA assays; YL performed animal models and flow cytometry; XZ and YH analyzed data and revised the manuscript; LZ, NN and YZ designed experiments, analyzed data, wrote the manuscript and provided overall supervision.

Author information

Author notes

    • Bo Sun
    • , Linnan Zhu
    • , Yaling Tao
    • , Hai-Xi Sun
    •  & Yang Li

    These authors contributed equally as co-first authors.

Affiliations

  1. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China

    • Bo Sun
    • , Linnan Zhu
    • , Yaling Tao
    • , Hai-Xi Sun
    • , Yang Li
    • , Peng Wang
    • , Yuzhu Hou
    • , Yang Zhao
    •  & Yong Zhao
  2. Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100101, China

    • Xiaodong Zhang
  3. Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China

    • Lianfeng Zhang
  4. Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China

    • Ning Na

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The authors declare no conflict of interest.

Corresponding authors

Correspondence to Lianfeng Zhang or Ning Na or Yong Zhao.

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https://doi.org/10.1038/cmi.2017.163

Supplementary Information for this article can be found on the Cellular & Molecular Immunology website (http://www.nature.com/cmi)