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Clinical & Experimental Allergy

Direct comparison of the dynamics of IL-25- and ‘allergen’-induced airways inflammation, remodelling and hypersensitivity in a murine asthma model

Authors

  • X. J. Yao,

    1. the Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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    • These authors contributed equally to this work.
  • K. W. Huang,

    1. the Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University & Beijing Institute of Respiratory Medicine, Beijing, China
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    • These authors contributed equally to this work.
  • Y. Li,

    1. the Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University & Beijing Institute of Respiratory Medicine, Beijing, China
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  • Q. Zhang,

    1. the Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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  • J. J. Wang,

    1. the Department of Laboratory Animal Sciences, Capital Medical University, Beijing, China
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  • W. Wang,

    1. the Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University & Beijing Institute of Respiratory Medicine, Beijing, China
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  • J. Liu,

    1. the Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
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  • Z. Lv,

    1. the Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
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  • Y. Q. An,

    1. the Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
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  • Y. Z. Ding,

    1. the Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
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  • C. J. Corrigan,

    1. Division of Asthma, Allergy & Lung Biology, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, UK
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  • W. Wang,

    Corresponding author
    1. the Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
    • Correspondence:

      Wei Wang or Sun Ying, the Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. E-mails: wy_robin@ccmu.edu.cn or ying.sun@kcl.ac.uk and Yongchang Sun, the Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China. E-mail: suny@ccmu.edu.cn

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  • Y. C. Sun,

    Corresponding author
    1. the Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China
    • Correspondence:

      Wei Wang or Sun Ying, the Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. E-mails: wy_robin@ccmu.edu.cn or ying.sun@kcl.ac.uk and Yongchang Sun, the Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China. E-mail: suny@ccmu.edu.cn

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  • S. Ying

    Corresponding author
    1. the Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
    2. Division of Asthma, Allergy & Lung Biology, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, UK
    • Correspondence:

      Wei Wang or Sun Ying, the Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. E-mails: wy_robin@ccmu.edu.cn or ying.sun@kcl.ac.uk and Yongchang Sun, the Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China. E-mail: suny@ccmu.edu.cn

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Summary

Background

Interleukin-25 has been implicated in the pathogenesis of asthma from studies on human asthmatics and in murine asthma models.

Objectives

In this study, we hypothesized that chronic exposure of the airways to IL-25 alone is able to induce pathogenic changes observed in animal models of asthma.

Methods

We performed a detailed comparison of the dynamics of development of cellular infiltration, cytokine expression and airways remodelling and hyperresponsiveness in mice sensitized and challenged with OVA, a classical model of allergic asthma and those exposed to IL-25 alone.

Results

Intranasal challenge of BALB/c mice with IL-25 alone induced a delayed (compared with OVA-challenge), predominantly eosinophilic and lymphocytic infiltration into the airways lumen, along with increased production of Th2-type cytokines, chemokines and collagen, secretion of epithelial mucus, goblet cell hyperplasia, deposition of subepithelial collagen, airways smooth muscle cell hyperplasia and angiogenesis. Correspondingly, IL-25 as well as OVA challenge both induced airways hyperresponsiveness and increased lung tissue damping. In contrast, IL-25 exposure did not increase IgE or IgG1 production.

Conclusions and Clinical Relevance

The data suggest that chronic airways exposure to IL-25 alone is sufficient to induce allergen- and IgE-independent, asthma-like airways inflammation, remodelling and hyperresponsiveness in mice. Thus, IL-25 is a key molecular target in asthma, irrespective of the coexistence of IgE-dependent mechanisms.

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