Chronic lung diseases asthma and COPD contribute substantially to global disease burden. The lung epithelium plays a crucial role in the development and progression of asthma and COPD, as its phenotype has been shown to be altered in both diseases. Lung epithelial cells encounter exogenous stimuli such as smoking and allergens, but also with endogenous factors derived from immune and stromal cell activation. How these factors might predispose the airway epithelium in chronic lung diseases is currently unclear, even though the lung epithelium could be a major vantage point for treatments.
In this thesis of Jelmer Vlasma, we investigate how exogenous and endogenous stimuli affect lung epithelial cell differentiation and repair in the context of chronic lung diseases asthma and COPD. We find in the context of asthma, lung epithelial cells respond strongly to immune cell-derived factors, whereas allergens result in a minimal response. In epithelial cells from patients with asthma, the response to the endogenous factor is augmented. In the context of COPD, we observe that smoke exposure prolongs a viral immune response in vivo.
Additionally, we identify the factor RANKL as a mediator of cell death, resulting in an expansion of several lung epithelial cell types. Combined, results of this thesis aid our understanding of the contribution of individual factors to the development of altered lung epithelia in COPD and asthma. For patients, we provide insight into potential pathways that are targetable for treatment and can affect fundamental disease mechanisms.
