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

Autor: Carla P. Jones, Gaynor A. Campbell, Andrew N. J. McKenzie, Devika Sawant, Lisa G. Gregory, Clare M. Lloyd, Simone A. Walker, Kate H C Gowers
Rok vydání: 2012
Předmět:
Pulmonary and Respiratory Medicine
Thymic stromal lymphopoietin
Angiogenesis
Inflammation
Smad2 Protein
Sensitivity and Specificity
Mice
Random Allocation
03 medical and health sciences
0302 clinical medicine
Airway Epithelium
medicine
Animals
Humans
Progenitor cell
Allergic lung disease
Cells
Cultured
030304 developmental biology
House dust mite
Mice
Inbred BALB C
0303 health sciences
biology
business.industry
Interleukins
Biopsy
Needle
Pyroglyphidae
Interleukin
Fibroblasts
respiratory system
biology.organism_classification
Immunohistochemistry
Asthma
respiratory tract diseases
3. Good health
Disease Models
Animal
Asthma Mechanisms
Gene Expression Regulation
Respiratory Research
Immunology
Airway Remodeling
Respiratory epithelium
Female
Bronchial Hyperreactivity
medicine.symptom
business
Bronchoalveolar Lavage Fluid
030215 immunology
Transforming growth factor
Zdroj: Thorax
ISSN: 1468-3296
0040-6376
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: