title: Hepatic immune regulation and its involvement in viral hepatitis infection.
abstract: The liver has unique immune regulatory functions that promote the induction of tolerance rather than responses to antigens encountered locally. These functions are mediated by local expression of coinhibitory receptors and immunosuppressive mediators that help prevent overwhelming tissue damage. Over the years, we have gained more insight into the local regulatory cues that determine the functional complexity of immune responses regulated locally in the liver. Both the unique hepatic microenvironment and the particular liver sinusoidal cell populations, in addition to hepatocytes, actively modulate immune responses locally in the liver and thereby determine the outcome of hepatic immune responses. This is of high biological and clinical relevance in hepatitis B virus and hepatitis C virus infections, which can cause acute and persistent infections associated with chronic inflammation in humans that eventually progress to cirrhosis and hepatocellular carcinoma. Here, we review current knowledge about the balance between immunity and tolerance in the liver and how this may affect our understanding of the determinants of hepatitis B virus and hepatitis C virus clearance, persistence, and virus-induced liver disease.
authors.affiliation: Institute of Molecular Immunology, Technische Universität München and Institutes of Molecular Medicine and Experimental Immunology, Universität Bonn, Bonn. Electronic address: knolle@uni-bonn.de.
authors.forename: Percy A
authors.initials: PA
authors.lastname: Knolle
authors.affiliation: Department of Medicine, Clinic for Gastroenterology, Hepatology, Endocrinology, Infectious Diseases, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Thimme
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D016174:Hepacivirus / Q000187:drug effects / Q000276:immunology*; D006509:Hepatitis B / Q000276:immunology* / Q000628:therapy / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000628:therapy / Q000821:virology; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy / Q000379:methods; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology
chemical_list: D000998:Antiviral Agents
keywords: Co-Inhibitory Molecules; Immune Exhaustion; Persistent Viral Infection; T-cell Immunity