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

Abstract

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.

• Authors: X J Yao, K W Huang, Y Li, Q Zhang, J J Wang, W Wang, J Liu, Z Lv, Y Q An, Y Z Ding, C J Corrigan, W Wang, Y C Sun, S Ying
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 44 Issue 5 Pg. 765-77 ( 2014) ISSN: 1365-2222 [Electronic] England
• PMID: 24575868 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Allergens
• Chemokines
• Cytokines
• Extracellular Matrix Proteins
• Immunoglobulin G
• Interleukins
• Mydgf protein, mouse
• Immunoglobulin E

Topics

• Airway Remodeling (immunology)
• Allergens (administration & dosage, immunology)
• Animals
• Asthma (immunology, metabolism, pathology)
• Chemokines (metabolism)
• Cytokines (metabolism)
• Disease Models, Animal
• Eosinophilia (immunology)
• Extracellular Matrix Proteins (metabolism)
• Female
• Goblet Cells (immunology, pathology)
• Hyperplasia
• Hypertrophy
• Immunoglobulin E (immunology)
• Immunoglobulin G (immunology)
• Inflammation (immunology, pathology)
• Interleukins (administration & dosage, immunology)
• Lung (immunology, pathology)
• Mice
• Muscle, Smooth (pathology)