Fig. 9.

Model of pIgR regulation in CF lung. First, accumulation of misfolded F508del-CFTR (CFTR*) is responsible for ER stress. Consequently, activation of UPR is able to downregulate SC and S-IgA secretion. Second, Pa infection modulates this pathway (orange arrows). Pa drives host IL-17 response which stimulates PIGR expression and further increases ER stress and UPR activation.[43,53] In addition, if ER stress caused by Pa infection becomes insufficiently counterbalanced by UPR activation, it may contribute to IgA upregulation, as previously shown.[45] CFTR, cystic fibrosis transmembrane regulator; UPR, unfolded protein response; SC, secretory component; S-IgA, secretory immunoglobulin A; d-IgA, dimeric immunoglobulin A; Pa, Pseudomonas aeruginosa; IL-17, interleukin 17; pIgR, polymeric immunoglobulin receptor.