Impaired airway immunoglobulin A immunity and epithelial differentiation in cystic fibrosis

In cystic fibrosis (CF), recurrent pulmonary infections suggest lung impaired mucosal immunity. The epithelium and the secretion of immunoglobulin A (IgA) by polymeric immunoglobulin receptor (pIgR) are major lines of mucosal defence. Therefore, this thesis aimed at assessing airway epithelial function (IgA secretion) and differentiation in CF. We observed an enhanced bronchoepithelial pIgR and IgA production in the CF lung, indicating upregulated humoral mucosal immunity due to Th17 host immune response against infection. By contrast, in the absence of infection, cell and animal experiments displayed a negative regulation of pIgR expression upon CFTR F508del mutation, associated with unfolded protein response. We also showed a ciliated cell defect and several signatures of impairment of the airway epithelium integrity, including epithelial-to-mesenchymal transition, in CF lung and cell. In conclusion, this thesis reveals in CF a complex interplay between dedifferentiated epithelial cells and (Pseudomonas aeruginosa) infection, which connects CFTR dysfunction, unfolded protein response activation, and a (Th17) host immune response to IgA secretion in the lung.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 202