Transcytosis route mediates rapid delivery of intact antibodies to draining lymph nodes
Open accessAbstract
Lymph nodes (LNs) filter lymph to mount effective immune responses. Small soluble lymph-borne molecules from the periphery enter the draining LNs via a reticular conduit system. Intact antibodies and other larger molecules, in contrast, are physically unable to enter the conduits, and they are thought to be transported to the LNs only within migratory DCs after proteolytic degradation. Here, we discovered that lymph-borne antibodies and other large biomolecules enter within seconds into the parenchyma of the draining LN in an intact form. Mechanistically, we found that the uptake of large molecules is a receptor-independent, fluid-phase process that takes place by dynamin-dependent vesicular transcytosis through the lymphatic endothelial cells in the subcapsular sinus of the LN. Physiologically, this pathway mediates a very fast transfer of large protein antigens from the periphery to LN-resident DCs and macrophages. We show that exploitation of the transcytosis system allows enhanced whole-organ imaging and spatially controlled lymphocyte activation by s.c. administered antibodies in vivo. Transcytosis through the floor of the subcapsular sinus thus represents what we believe to be a new physiological and targetable mode of lymph filtering.
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SCS floor LECs participate in the transport of soluble antigens into the lymph node parenchyma through receptor-independent antigen transcytosis and through guarding proteinaceous diaphragms through which antigens access a collagenous reticular conduit system.
“SCS floor LECs participate in the transport of soluble antigens into the lymph node parenchyma both through the process of receptor-independent antigen transcytosis and through their function as guardians of proteinaceous diaphragms present in the SCS floor through which antigens gain access to a collagenous reticular conduit system (124, 125).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [124]
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- Authors
- Kähäri, L., Fair-Mäkelä, R., Auvinen, K., Rantakari, P., Jalkanen, S., Ivaska, J., & Salmi, M.
- Affiliations
- University of Turku (FI)
- Corresponding author
- Salmi, Marko
- Venue
- Journal of Clinical Investigation
- Published
- 2019-06-24
- Volume
- 129
- Issue
- 8
- Pages
- 3086-3102
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC6668680
- OpenAlex
- W2951902689
- Cited by
- 74
- References
- 64
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 12 · 2023: 8 · 2022: 9 · 2021: 12 · 2020: 12 · 2019: 4 · 2018: 1
- FWCI
- 3.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UTUPub (University of Turku) (submittedVersion)
- Funders
- Academy of Finland, Juselius Foundation (312517,303802,276401,315947,16032016)
- Topics
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- transcytosis, lymphatic endothelial cells, subcapsular sinus, fluid-phase uptake, dendritic cells, macrophages, lymphocyte activation, whole-organ imaging
- MeSH terms
- Animals, Antibodies, Dendritic Cells, Lymph Nodes, Macrophages, Mice, Inbred BALB C, Mice, Knockout, Protein Transport, Endothelial Cells, Mice, Transcytosis
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