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Direct comparison of the dynamics of IL ‐25‐ and ‘allergen’‐induced airways inflammation, remodelling and hypersensitivity in a murine asthma model
Author(s) -
Yao X. J.,
Huang K. W.,
Li Y.,
Zhang Q.,
Wang J. J.,
Wang W.,
Liu J.,
Lv Z.,
An Y. Q.,
Ding Y. Z.,
Corrigan C. J.,
Wang W.,
Sun Y. C.,
Ying S.
Publication year - 2014
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12298
Subject(s) - inflammation , immunology , allergen , asthma , allergic inflammation , medicine , allergy
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 IgG 1 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.