IL-25 drives remodelling in allergic airways disease induced by house dust mite. Issue 1 (23rd October 2012)

• Record Type: Journal Article
• Authors: Gregory, Lisa G; Jones, Carla P; Walker, Simone A; Sawant, Devika; Gowers, Kate H C; Campbell, Gaynor A; McKenzie, Andrew N J; Lloyd, Clare M
• Is Part Of: Thorax. Volume 68:Issue 1(2013)
• Page Start: 82
• Page End: 90
• Publication Date: 2012-10-23
• Subjects: Airway Epithelium -- Allergic lung disease -- Asthma -- Asthma Mechanisms; Chest -- Diseases -- Periodicals; Thorax; Chest -- Diseases; Periodicals; Periodicals; 617.54
• DOI: 10.1136/thoraxjnl-2012-202003
• Languages: English
• ISSNs: 0040-6376

Abstract

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.