title: Distinct kinetics and dynamics of cross-presentation in liver sinusoidal endothelial cells compared to dendritic cells.
abstract: Cross-presentation is an important function of immune competent cells, such as dendritic cells (DCs), macrophages, and an organ-resident liver cell population, i.e., liver sinusoidal endothelial cells (LSECs). Here, we characterize in direct comparison to DCs the distinct dynamics and kinetics of cross-presentation employed by LSECs, which promote tolerance induction in CD8 T cells. We found that LSECs were as competent in cross-presenting circulating soluble antigen ex vivo as DCs at a per-cell basis. However, antigen uptake in vivo was 100-fold more pronounced in LSECs, indicating distinct mechanisms of cross-presentation. In contrast to mannose-receptor-mediated antigen uptake and routing into stable endosomes dedicated to cross-presentation in DCs, we observed distinct antigen-uptake and endosomal routing with high antigen turnover in LSECs that resulted in short-lived cross-presentation. Receptor-mediated endocytosis did not always lead to cross-presentation, because immune-complexed antigen taken up by the Fc-receptor was not cross-presented by LSECs, indicating that induction of CD8 T cell tolerance by LSECs is impaired in the presence of preexisting immunity.
  
  
  CONCLUSIONS
  These results provide a mechanistic explanation how organ-resident LSECs accommodate continuous scavenger function with the capacity to cross-present circulating antigens using distinct kinetics and dynamics of antigen-uptake, routing and cross-presentation compared to DCs.
authors.affiliation: Institute of Molecular Medicine and Experimental Immunology, University Hospital Bonn, Bonn, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Schurich
authors.forename: Jan P
authors.initials: JP
authors.lastname: Böttcher
authors.forename: Sven
authors.initials: S
authors.lastname: Burgdorf
authors.forename: Patrick
authors.initials: P
authors.lastname: Penzler
authors.forename: Silke
authors.initials: S
authors.lastname: Hegenbarth
authors.forename: Michaela
authors.initials: M
authors.lastname: Kern
authors.forename: Andreas
authors.initials: A
authors.lastname: Dolf
authors.forename: Elmar
authors.initials: E
authors.lastname: Endl
authors.forename: Joachim
authors.initials: J
authors.lastname: Schultze
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Wiertz
authors.forename: Dirk
authors.initials: D
authors.lastname: Stabenow
authors.forename: Christian
authors.initials: C
authors.lastname: Kurts
authors.forename: Percy
authors.initials: P
authors.lastname: Knolle
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis / Q000502:physiology; D042783:Endothelial Cells / Q000276:immunology*; D037181:Lectins, C-Type / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D000941:Antigens; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D010047:Ovalbumin