Liver disease (CFLD) can compromise survival and quality of life of the CF patients and unfortunately a cure is not yet available. The cause of liver damage was thought to be the impaired ability of specialized liver cells to produce bile in the proper amount and quality. Researchers in FFC#18/2012 project originally described that lack of CFTR has a profound impact on the defense mechanisms that normally protect the biliary system from infections (Toll-like receptor innate immunity). Now, they hypothize that CFTR participates in the regulation of TLRs signaling and that a correct therapeutic approach should aim at controlling inflammation in biliary epithelial cells. Aim of this project is to generate a new cellular model, closer to the human disease than animal model, using human induced pluripotent stem cells (iPSC). iPSCs from a CF patient carrying the CFTR mutation ΔF508 will differentiate into epithelial biliary cells and will be used to determine the impact of CFTR-ΔF508 mutation on TLR4 responses and the therapeutic benefit of interfering with several signaling proteins involved in epithelial innate responses.