Role of IL-33 and SERPINB4 in the exacerbations of airway inflammation, induced by viral- or bacterial-derived pathogens

Patients with a severe airway inflammation have frequent periods in which the symptoms of the disease increase. Particularly human rhinoviruses and Staphylococcus aureus can trigger the exacerbations of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The scientific objective of this project is to gain more insight in the still unknown molecular pathways of the exacerbations. We hypothesize that serine protease-like protein D (SplD), derived from S. aureus, and HRV 3C proteases lead to an activation of IL-33. IL-33 is a crucial cytokine in the development of inflammation. Next, we speculate that also SERPINB4 plays a role in exacerbations. SERPINB4 is a serine protease inhibitor, that is upregulated in CRSwNP patients. It inhibits the degradation of IL-33 and prevents cell death of immune cells, probably leading to a persistent inflammation. At last, the use of nanoparticles for gene silencing of IL33 or SERPINB4 in order to prevent these exacerbations will also be investigated.