Regulation and cross-talk between environmental triggers of local immune responses in airway epithelial cells

Airway epithelium plays an important role in the regulation of the innate immune responses and in this thesis I investigated the role of epithelial cells in the local regulation of inflammatory responses in relation to allergy and other airway diseases. I studied the commonalities and differences of the pro-inflammatory responses induced in airway epithelial cells by viral infections and by allergens and a role of the EGR-1 and DUSP-1 genes in the regulation of these responses. To mimic the real life constant exposure to variety of microbial challenges, I explored the functional interaction between TLR-3 and TLR-2 in primary nasal epithelial cells and sought whether the functional collaboration of TLRs can be extended to lower airways, in the lung epithelium. Moreover, I demonstrated how to overcome the natural occurring tolerance of nasal epithelium to LPS or P. aeruginosa by co-stimulating the cells with immunoglobulin G. Since the local tissue environment consists of epithelial cells that co-operate directly or indirectly with other immune cells, I explored the importance of epithelium in polarization and activation of other immune cells in pathogenesis of upper airway diseases. I showed that nasal polyps of patients with chronic rhinosinusitis, a typical type-2 mediated disease are enriched with type 2 innate lymphoid cells (ILC2). Moreover, I demonstrated the evidence that nasal epithelium is the major source of the type 2 skewing cytokines necessary for ILC2s activation in chronic rhinosinusitis with nasal polyps.