4 However, the role of Th17 responses in various viral infections is not entirely clear: while studies in https://www.selleckchem.com/products/Adriamycin.html some models suggest that Th17 is important in recruiting innate defense to mucosal sites in viral infection,8 others have suggested that IL-17 may play a role in increasing the immunopathology associated with viral infection.9 In addition to
their role in host defense, Th17 responses are also thought to play a part in the pathogenesis of a variety of immune mediated pathologies, including psoriasis, rheumatoid arthritis and Crohn’s disease (reviewed in Miossec et al.3 and Crome et al.4). Indeed, therapy with neutralizing antibodies against the common p40 chain of IL-12 and IL-23, the latter of which is required for development of Th17 responses, has yielded promising results in studies in a range of conditions.3,4
On this basis, such antibodies have been approved for use in psoriasis in the US and Europe, with ongoing studies in other conditions, in particular Crohn’s disease. Given the explosion of work on this cellular subset, it is unsurprising that interest in Th17 cells has also extended to studies of their role in the pathogenesis of a variety of liver conditions. Evidence for a role of IL-17 and Th17 cells has been obtained in a number of mouse models of liver injury, including schistosomal infection, primary biliary cirrhosis, and halothane induced hepatitis (recently reviewed in Hammerich et al.10). Metalloexopeptidase Studies in human liver
PARP inhibitor disease also suggest a role for the Th17 response in autoimmune liver disease, alcoholic liver disease, non-alcoholic steatohepatitis, and hepatocellular carcinoma. Th17-mediated immunity has also been an area of interest as regards its roles both in immunity to hepatotropic viruses and its part in the pathogenesis of liver disease in chronic infection with the hepatitis B and C viruses (HBV and HCV). In terms of viral hepatitis, the role of Th17 cells has currently been best studied in chronic HBV infection. The frequency of Th17 cells in peripheral blood has been demonstrated to be increased in individuals with chronic hepatitis B, with a positive correlation with serum alanine aminotransferase (ALT).11 The frequency of Th17 cells in the peripheral blood has also been found to be higher in subjects with acute or chronic flares of hepatitis B than in those with stable hepatitis B.12 Th17 cells were also increased in the liver in chronic HBV, and increases in Th17 frequencies were associated with viral load, ALT, and hepatitis activity index (HAI).12 In contrast, in another study, while increased numbers of Th17 cells correlated with ALT, a relationship with HBV DNA was not seen.13 The frequency of IL-17 producing cells in the chronically HBV-infected liver has also been shown to increase with higher Child–Pugh grade.