TY - UNPB
T1 - Allergen-induced airway matrix remodelling in mice can be prevented or reversed by targeting chitinase-like proteins
AU - Parkinson, James E
AU - Adamson, Antony
AU - MacDonald, Andrew S
AU - Allen, Judith E
AU - Sutherland, Tara E
N1 - The authors thank Stella Pearson and Brian Chan for their technical support, Peter Cook for advice on flow cytometry, and Hannah Tompkins for critically reading the manuscript. We also thank the Flow Cytometry, Histology and Biological Services core facilities at the University of Manchester.
PY - 2023/8/21
Y1 - 2023/8/21
N2 - 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.
AB - 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.
UR - https://doi.org/10.1101/2023.08.18.553857
U2 - 10.1101/2023.08.18.553857
DO - 10.1101/2023.08.18.553857
M3 - Preprint
BT - Allergen-induced airway matrix remodelling in mice can be prevented or reversed by targeting chitinase-like proteins
PB - bioRxiv
ER -