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CRISPR/Cas9- or siRNA-mediated down-regulation of IRF8 prevented changes of acid ceramidase, ceramide and sphingosine in CF epithelial cells and restored resistance to Pseudomonas aeruginosa infections, which is one of the most important and common pathogens in lung infection of patients with CF. These studies indicate that CFTR-deficiency causes a down-regulation of acid ceramidase via up-regulation of IRF8, which is a central pathway to control infection susceptibility of CF cells.Epigenetic modifications have emerged as critical reg