Developmental research on dendritic cell-based immunotherapy against chronic hepatitis C and hepatocellular carcinoma

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In hepatitis C virus (HCV) infection, it is well known that the impaired function of dendritic cells (DC) is critically involved in the development of liver disease as well as resistance to anti-viral therapy, such as a combination of peg-interferon-a and ribavirin. We demonstrated in this research project that myeloid DC (MDC) are functionally impaired in the production of type-I IFN and IL-12 in response to Toll-like receptor (TLR) signaling, of which is partly due to reduced expression of TRIF and TRAF6 adaptor molecules. In addition, the treatment of MDC with HCV NS3/4A protease inhibitor restored MDC of stimulatory capacity for CD4+ T cells. Therefore, we demonstrate that MDC could be served as a therapeutic target in order to enhance anti-HCV immune reactions.