Chronic obstructive pulmonary disease (COPD) is a lung disease that affects the airways and alveoli. Central to its pathology are chronic inflammation and abnormalities in the extracellular matrix (ECM) within the lungs. The dynamic interplay between immune cells and ECM often generates ECM fragments, increasingly recognised as potential biomarkers of disease endotypes and monitoring progression. However, the impact of aberrant ECM on immune cell responses in COPD remains underexplored.
In this thesis of Mugdha Joglekar, we aimed to further characterise lung ECM in COPD and investigate its crosstalk with immune cells. We utilised native human lung tissues or innovative in vitro models derived from them. Our study highlighted differential composition of lung ECM as a distinct feature of severe COPD. We also noted a higher degree of crosslinking and altered proportions of organised to disorganised collagens in COPD lung tissue. Further, the applicability of protein fragments as markers of COPD were also investigated, where calprotectin (a major cytosolic component of neutrophils) emerged as a promising biomarker for milder COPD, warranting further exploration of its role in disease pathology. Our study using decellularised lung ECM hydrogels showed that COPD microenvironment activates human lung fibroblasts leading to contraction and increased stiffness of the microenvironment. The addition of monocytes, however, mitigates this response suggesting a protective role.
Overall, this thesis underlined the importance of characterising the ECM in disease and its role in regulating cellular responses. Several novel research avenues for understanding disease mechanisms and identifying clinically relevant COPD biomarkers were also identified.
