Compared to healthy controls

or primary biliary cirrhosis patients, PBMCs from PSC patients manifested significantly higher frequencies of Th17 and Th1/Th17 cells after pathogen stimulation. The highest frequencies of Th17 cells were detected after stimulation with Candida albicans, a pathogen that has been linked to disease progression. Immunohistochemically, IL-17A-expressing lymphocytes were detected within the periductal areas of PSC patients. Th17 induction was also noted after stimulation of Toll-like receptor 5 or 7, but not of other pattern recognition selleck chemical receptors tested, pointing to signaling pathways potentially involved in Th17 induction in PSC. Conclusion: We demonstrate an increased Th17 response to microbial stimulation in patients with

PSC. These data should prompt further studies investigating the link between pathogen responses, Torin 1 in vivo inflammation, and fibrosis in patients with PSC. (Hepatology 2013;53:1084–1093) Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by inflammation and fibrosis of the intrahepatic and/or extrahepatic bile ducts, finally leading to liver cirrhosis and end-stage liver disease.[1] To date, there is no medical treatment with a proven benefit on the progressive course of the disease. A key characteristic of PSC is the association with inflammatory bowel disease (IBD), mostly an ulcerative colitis-like disease, in approximately two thirds of the cases. A dysregulated response to pathogen stimulation may contribute to the immune activation in PSC, as has been postulated for the associated IBD.[2, 3] From the clinical point of view, it is Resveratrol well known that dominant biliary strictures in patients with PSC are associated with bacterial cholangitis, and that bacterial and, especially, fungal cholangitis may accelerate the progression of PSC.[4, 5] A higher rate of positive bacterial cultures could be obtained from bile of explanted livers from PSC patients, as compared to patients with primary biliary

cirrhosis (PBC).[6] In addition, treatment with the antibiotic, metronidazole, resulted in some beneficial effects on liver histology, as compared to treatment with ursodeoxycholic acid (UDCA) alone.[7] T helper (Th)17 cells, which are characterized by the signature cytokine, interleukin (IL)-17A, play an important role in the defense against extracellular bacteria and fungi,[8, 9] particularly at epithelial and mucosal surfaces.[10] Interestingly, functional as well as genetic evidence suggests a role of Th17 cells for the pathogenesis of IBD.[11] Th17 cells have also been implicated in the pathogenesis of several human autoimmune diseases, such as lupus erythematodes, multiple sclerosis, psoriasis, and rheumatoid arthritis.