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Kinetics of the accumulation of group 2 innate lymphoid cells in IL-33-induced and IL-25-induced murine models of asthma: a potential role for the chemokine CXCL16

Cellular & Molecular Immunology volume 16, pages 75–86 (2019)Cite this article

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Abstract

ILC2s are implicated in asthma pathogenesis, but little is known about the mechanisms underlying their accumulation in airways. We investigated the time course of ILC2 accumulation in different tissues in murine models of asthma induced by a serial per-nasal challenge with ovalbumin (OVA), house dust mice (HDM), IL-25 and IL-33 and explored the potential roles of ILC2-attracting chemokines in this phenomenon. Flow cytometry was used to enumerate ILC2s at various time points. The effects of cytokines and chemokines on ILC2 migration were measured in vitro using a chemotaxis assay and in vivo using small animal imaging. Compared with saline and OVA challenge, both IL-25 and IL-33 challenge alone induced significant accumulation of ILC2s in the mediastinal lymph nodes, lung tissue and bronchoalveolar lavage fluid of challenged animals, but with a distinct potency and kinetics. In vitro, IL-33 and CXCL16, but not IL-25 or CCL25, directly induced ILC2 migration. Small animal in vivo imaging further confirmed that a single intranasal provocation with IL-33 or CXCL16 was sufficient to induce the accumulation of ILC2s in the lungs following injection via the tail vein. Moreover, IL-33-induced ILC2 migration involved the activation of ERK1/2, p38, Akt, JNK and NF-κB, while CXCL16-induced ILC2 migration involved the activation of ERK1/2, p38 and Akt. These data support the hypothesis that epithelium-derived IL-25 and IL-33 induce lung accumulation of ILC2s, while IL-33 exerts a direct chemotactic effect in this process. Although ILC2s express the chemokine receptors CXCR6 and CCR9, only CXCL16, the ligand of CXCR6, exhibits a direct chemoattractant effect.

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Acknowledgements

We acknowledge financial support from the National Natural Science Foundation of China (81373177, 81471594, and 81700026).

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Authors and Affiliations

  1. Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, P.R. China

    Yan Li, Shihao Chen, Yiran Yang, Xiwen Chen, Zhe Lv, Linjie Yuan, Ping Huang, Wei Wang & Sun Ying

  2. Department of Laboratory Animal Sciences, Capital Medical University, Beijing, China

    Yafei Chi & Jingjing Wang

  3. Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University and Beijing Institute of Respiratory Medicine, Beijing, China

    Huating Wang & Kewu Huang

  4. Faculty of Life Sciences & Medicine, School of Immunology and Microbial Sciences, Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, London, UK

    Chris J. Corrigan

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Correspondence to Wei Wang or Sun Ying.

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Li, Y., Chen, S., Chi, Y. et al. Kinetics of the accumulation of group 2 innate lymphoid cells in IL-33-induced and IL-25-induced murine models of asthma: a potential role for the chemokine CXCL16. Cell Mol Immunol 16, 75–86 (2019). https://doi.org/10.1038/s41423-018-0182-0

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