Allergen-induced airway matrix remodelling in mice can be prevented or reversed by targeting chitinase-like proteins

Abstract Chitinase-like proteins (CLPs) are biomarkers of inflammation and airway remodelling in asthma, yet their direct contribution towards disease pathogenesis is unknown. Using a mouse model of allergen-induced type 2/type 17 airway inflammation we sought to directly investigate the role of the murine CLPs Ym1 and Ym2 during chronic lung pathology. Data demonstrated distinct chronic inflammatory roles for Ym2, IL-13, and IL-17a signalling pathways. Notably, only CLPs were key for initiating the pathogenic accumulation and re-organisation of the pulmonary extracellular matrix (ECM) environment. Furthermore, inhibition of CLPs after chronic pathology developed, reversed airway remodelling independently of chronic inflammation. These studies disentangle chronic IL-13 and IL-17a signalling from the development of allergic airway remodelling and instead highlight a central role for CLPs, which provides new avenues to therapeutically target aberrant ECM accumulation.