title: The role of hepatic immune regulation in systemic immunity to viral infection.
abstract: The liver has particular immune functions attributed by its unique microenvironment and its liver-resident cell populations. During autoimmunity and viral hepatitis, the liver serves as target for effector responses of immune cells. However, skewing of effector T cell functions through tolerogenic liver-resident antigen-presenting cells and through the immune regulatory hepatic microenvironment. Importantly, the liver also participates in shaping systemic antigen-specific immunity. Local antigen-presenting cell populations, in particular liver sinusoidal endothelial cells (LSECs), cross-present soluble, circulating or hepatocyte-derived antigens to naïve CD8 T cells. Upon priming by cross-presenting LSECs, naïve CD8 T cells develop into a unique population of antigen-experienced memory-like T cell population that can be reactivated in an inflammatory context to protect against infection with viruses or bacteria. Furthermore, upon prolonged inflammatory TNF-dependent signaling, the induction of intrahepatic myeloid cell aggregates for T cell population expansion (iMATEs) is observed in liver tissue. iMATEs are formed by inflammatory monocytes developing into dendritic cells and function to attract recently activated CD8 T cells. Those CD8 T cells located within the cocoon-like iMATE structure show strong proliferation initiated by co-stimulatory signaling. Locally expanded CD8 T cells are key to control acute and chronic viral infections. The mechanistic understanding of local hepatic T cell priming and local expansion of effector CD8 T cells will help to develop novel therapeutic vaccination strategies.
authors.affiliation: Institute of Molecular Immunology, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675, Munich, Germany, Percy.Knolle@TUM.de.
authors.forename: Percy A
authors.initials: PA
authors.lastname: Knolle
authors.forename: Jan
authors.initials: J
authors.lastname: Böttcher
authors.forename: Li-Rung
authors.initials: LR
authors.lastname: Huang
mesh_terms: D056704:Adaptive Immunity; D001419:Bacteria / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008099:Liver / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology*; D014780:Viruses / Q000276:immunology