IL-25 drives remodelling in allergic airways disease induced by house dust mite
- Lisa G Gregory1,
- Carla P Jones1,
- Simone A Walker1,
- Devika Sawant1,
- Kate H C Gowers1,
- Gaynor A Campbell1,
- Andrew N J McKenzie2,
- Clare M Lloyd1
- 1Leukocyte Biology Section, National Heart and Lung Institute, Imperial College London, London, UK
- 2MRC Laboratory of Molecular Biology, Cambridge, UK
- Correspondence to Professor Clare M Lloyd, National Heart and Lung Institute, Imperial College, South Kensington, London SW7 2AZ, UK;
- Received 11 April 2012
- Revised 21 August 2012
- Accepted 10 September 2012
- Published Online First 23 October 2012
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.
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