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Updated: Jun 21, 2026
Isolation and Characterization of Mouse Primary Liver Sinusoidal Endothelial Cells
Published on: December 16, 2021
Distinct kinetics and dynamics of cross-presentation in liver sinusoidal endothelial cells compared to dendritic
Anna Schurich1, Jan P Böttcher, Sven Burgdorf
1Institute of Molecular Medicine and Experimental Immunology, University Hospital Bonn, Bonn, Germany.
Insights
Liver sinusoidal endothelial cells (LSECs) efficiently uptake antigens in vivo, differing from dendritic cells (DCs). LSECs present antigens with distinct kinetics, impacting CD8 T cell tolerance induction.
Area of Science:
- Immunology
- Cell Biology
- Hepatology
Background:
- Cross-presentation is a critical immune function performed by antigen-presenting cells like dendritic cells (DCs).
- Liver sinusoidal endothelial cells (LSECs) are organ-resident cells with immune functions, including antigen presentation.
- Understanding LSEC cross-presentation is key to comprehending immune tolerance in the liver.
Purpose of the Study:
- To directly compare the dynamics and kinetics of cross-presentation between LSECs and DCs.
- To elucidate the mechanisms underlying antigen uptake and processing by LSECs for cross-presentation.
- To determine how LSEC cross-presentation influences CD8 T cell responses and immune tolerance.
Main Methods:
- Ex vivo characterization of antigen uptake and cross-presentation by LSECs and DCs.
- In vivo assessment of antigen distribution and cellular uptake.
- Analysis of endosomal antigen routing and turnover.
- Investigation of Fc-receptor mediated antigen uptake and cross-presentation.
Main Results:
- LSECs exhibit robust cross-presentation capacity comparable to DCs on a per-cell basis ex vivo.
- In vivo antigen uptake is significantly higher (100-fold) in LSECs compared to DCs, suggesting distinct uptake mechanisms.
- LSECs display unique antigen uptake and endosomal routing with rapid turnover, leading to transient cross-presentation.
- Immune-complexed antigens via Fc-receptors are not cross-presented by LSECs, potentially impairing tolerance induction in pre-existing immunity.
Conclusions:
- LSECs possess distinct antigen uptake, routing, and cross-presentation kinetics compared to DCs.
- These findings provide a mechanistic basis for how LSECs balance scavenger functions with antigen cross-presentation.
- LSEC's unique cross-presentation dynamics contribute to immune tolerance in the liver, with specific limitations in pre-existing immunity.
Unlabelled:
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.
Conclusion:
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.
