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Thorax. 2013 Jan;68(1):82-90. doi: 10.1136/thoraxjnl-2012-202003. Epub 2012 Oct 23.

IL-25 drives remodelling in allergic airways disease induced by house dust mite.

Author information

1
Leukocyte Biology Section, National Heart and Lung Institute, Imperial College London, London, UK.

Abstract

BACKGROUND:

Overexpression of the transforming growth factor β family signalling molecule smad2 in the airway epithelium provokes enhanced allergen-induced airway remodelling in mice, concomitant with elevated levels of interleukin (IL)-25.

OBJECTIVE:

We investigated whether IL-25 plays an active role in driving this airway remodelling.

METHODS:

Anti-IL-25 antibody was given to mice exposed to either inhaled house dust mite (HDM) alone, or in conjunction with an adenoviral smad2 vector which promotes an enhanced remodelling phenotype.

RESULTS:

Blocking IL-25 in allergen-exposed mice resulted in a moderate reduction in pulmonary eosinophilia and levels of T helper type 2 associated cytokines, IL-5 and IL-13. In addition, IL-25 neutralisation abrogated peribronchial collagen deposition, airway smooth muscle hyperplasia and airway hyperreactivity in control mice exposed to HDM and smad2-overexpressing mice. IL-25 was shown to act directly on human fibroblasts to induce collagen secretion. Recruitment of endothelial progenitor cells to the lung and subsequent neovascularisation was also IL-25 dependent, demonstrating a direct role for IL-25 during angiogenesis in vivo. Moreover, the secretion of innate epithelial derived cytokines IL-33 and thymic stromal lymphopoietin (TSLP) was completely ablated.

CONCLUSIONS:

In addition to modulating acute inflammation, we now demonstrate a role for IL-25 in orchestrating airway remodelling. IL-25 also drives IL-33 and TSLP production in the lung. These data delineate a wider role for IL-25 in mediating structural changes to the lung following allergen exposure and implicate IL-25 as a novel therapeutic target for the treatment of airway remodelling in asthma.

PMID:
23093652
PMCID:
PMC3534261
DOI:
10.1136/thoraxjnl-2012-202003
[Indexed for MEDLINE]
Free PMC Article
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