The magnitude of airway remodelling is not altered by distinct allergic inflammatory responses in BALB/c vs C57BL/6 mice, but matrix composition differs

Airway inflammation in response to allergens is heterogenous with variability in immune phenotypes observed across asthmatic patients. Whilst inflammation, specifically type 2 immune responses, are thought to directly contribute to airway remodelling and pathology in asthma, clinical data suggests that neutralising type 2 cytokines do not necessarily alter disease pathogenesis. Here we show, using a mouse model allergic airway inflammation, that both C57BL/6 and BALB/c mice develop mixed type 2 and type 17 inflammation. However, BALB/c mice develop much greater inflammatory responses than C57BL/6 mice, effects possibly explained by a reduction in pathways that regulate and maintain T cell activation in C57BL/6 mice, as shown by RNA transcript analysis. Chronic allergen exposure resulted in a similar degree of airway remodelling changes such as ECM deposition and increases in goblet cells and airway muscle mass between mouse strains. However, collagen subtype composition revealed increased collagen III around of the airways of C57BL/6 but not BALB/c mice. Furthermore, allergen-induced loss of basement membrane collagen IV was only observed in BALB/c mice. This study highlights a model of type 2/type 17 airway inflammation in mice whereby development of airway remodelling can occur in both BALB/c and C57BL/6 mice despite differences in immune response dynamics between strains. Importantly, compositional differences in the ECM between genetic strains of mice may help us better understand the relationships between lung function, remodelling and airway inflammation.