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  • Review Article
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Lymphatic endothelial cells of the lymph node

Nature Reviews Immunology volume 20, pages 566–578 (2020)Cite this article

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Abstract

The influx and efflux of cells and antigens to and from the draining lymph nodes largely take place through the subcapsular, cortical and medullary sinus systems. Recent analyses in mice and humans have revealed unexpected diversity in the lymphatic endothelial cells, which form the distinct regions of the sinuses. As a semipermeable barrier, the lymphatic endothelial cells regulate the sorting of lymph-borne antigens to the lymph node parenchyma and can themselves serve as antigen-presenting cells. The leukocytes entering the lymph node via the sinus system and the lymphocytes egressing from the parenchyma migrate through the lymphatic endothelial cell layer. The sinus lymphatic endothelial cells also orchestrate the organogenesis of lymph nodes, and they undergo bidirectional signalling with other sinus-resident cells, such as subcapsular sinus macrophages, to generate a unique lymphatic niche. In this Review, we consider the structural and functional basis of how the lymph node sinus system coordinates immune responses under physiological conditions, and in inflammation and cancer.

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Fig. 1: The lymphatic sinus systems of lymph nodes in mice and humans.
Fig. 2: Pathways mediating the transfer of macromolecules across the subcapsular floor.
Fig. 3: Leukocyte entry and exit through lymphatics in the lymph nodes.
Fig. 4: Lymphatic endothelial cells in organizing the lymph node niche.

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Acknowledgements

The authors thank A. Takeda for discussions. This work was supported by the Academy of Finland, Cancer Foundation Finland and Juselius Foundation.

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  1. MediCity Research Laboratory, University of Turku, Turku, Finland

    Sirpa Jalkanen & Marko Salmi

  2. Institute of Biomedicine, University of Turku, Turku, Finland

    Sirpa Jalkanen & Marko Salmi

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  1. Sirpa Jalkanen
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The authors contributed equally to all aspects of the article.

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Correspondence to Marko Salmi.

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Glossary

Fibroblastic reticular cells

(FRCs). Specialized reticular fibroblasts located in the T cell areas of lymph nodes and other secondary lymphoid organs that produce collagen-rich reticular fibres and form stromal networks and conduits that are important for the trafficking of immune cells.

High endothelial venules

Specialized venules that occur in secondary lymphoid organs, except the spleen. High endothelial venules allow continuous transmigration of lymphocytes as a consequence of the constitutive expression of adhesion molecules and chemokines on their luminal surface.

Extravasation cascade

The multistep process of leukocyte infiltration through the endothelium. This process proceeds through the stages of leukocyte rolling, adhesion, diapedesis and, finally, migration to the surrounding tissues.

B cell follicles

Aggregates of B cells in lymphoid tissues. They contain naive B cells, as well as activated, proliferating and maturing B cells in germinal centres. B cell follicles are contiguous with T cell zones.

Immunoproteasome

A form of proteasome with unique subunits. Immunoproteasome has distinct cleavage-site preferences, which may improve antigen presentation.

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Jalkanen, S., Salmi, M. Lymphatic endothelial cells of the lymph node. Nat Rev Immunol 20, 566–578 (2020). https://doi.org/10.1038/s41577-020-0281-x

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