Cited by 203Lymphatic System and DiseasesBarrier Structure and Function StudiesLymphatic Disorders and Treatments

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The endothelial protein PLVAP in lymphatics controls the entry of lymphocytes and antigens into lymph nodes

Rantakari, Pia, Auvinen, Kaisa, Jäppinen, Norma, Kapraali, Maria, Valtonen, Joona, Karikoski, Marika, Gerke, Heidi, Iftakhar-E-Khuda, Imtiaz, Keuschnigg, Johannes, Umemoto, Eiji, Tohya, Kazuo, Miyasaka, Masayuki, Elima, Kati, Jalkanen, Sirpa, Salmi, Marko·2015·Nature Immunology

DOI 10.1038/ni.3101

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Abstract

In the lymphatic sinuses of draining lymph nodes, soluble lymph-borne antigens enter the reticular conduits in a size-selective manner and lymphocytes transmigrate to the parenchyma. The molecular mechanisms that control these processes are unknown. Here we unexpectedly found that PLVAP, a prototypic endothelial protein of blood vessels, was synthesized in the sinus-lining lymphatic endothelial cells covering the distal conduits. In PLVAP-deficient mice, both small antigens and large antigens entered the conduit system, and the transmigration of lymphocytes through the sinus floor was augmented. Mechanistically, the filtering function of the lymphatic sinus endothelium was dependent on diaphragms formed by PLVAP fibrils in transendothelial channels. Thus, in the lymphatic sinus, PLVAP forms a physical sieve that regulates the parenchymal entry of lymphocytes and soluble antigens.

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Authors: Rantakari, P., Auvinen, K., Jäppinen, N., Kapraali, M., Valtonen, J., Karikoski, M., Gerke, H., Iftakhar-E-Khuda, I., Keuschnigg, J., Umemoto, E., Tohya, K., Miyasaka, M., Elima, K., Jalkanen, S., & Salmi, M.
Affiliations: University of Turku (FI)
Immunology Frontier Research Center, The University of Osaka (JP)
Kansai University of Health Sciences (JP)
Corresponding author: Salmi, Marko
ORCID: Rantakari, Pia
Valtonen, Joona
Karikoski, Marika
Gerke, Heidi
Umemoto, Eiji
Miyasaka, Masayuki
Jalkanen, Sirpa
Salmi, Marko
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2015-02-09
Volume: 16
Issue: 4
Pages: 386-396
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni.3101
OpenAlex: W1977274736
Cited by: 203
References: 51
Citations by year: 2026: 7 · 2025: 17 · 2024: 17 · 2023: 13 · 2022: 9 · 2021: 24 · 2020: 27 · 2019: 26 · 2018: 20 · 2017: 10 · 2016: 24 · 2015: 9
FWCI: 9.17
Type: journal article
Language: en
Update notices: erratum (2015-04-21)
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: Japan Society for the Promotion of Science
Topics: Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
Keywords: PLVAP, lymphatic endothelium, lymph nodes, lymphatic sinuses, lymphocyte transmigration, size-selective filtration
MeSH terms: Animals, Antigens, Carrier Proteins, Endothelium, Lymphatic, Female, Gene Expression Regulation, Lymph Nodes, Lymphocytes, Male, Membrane Proteins, Mice, Inbred BALB C, Mice, Inbred C57BL, Signal Transduction, Antigens, CD, Mice, Knockout, Lymphatic Vessels, Endothelial Cells, Caveolin 1, Mice, Transendothelial and Transepithelial Migration

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The endothelial protein PLVAP in lymphatics controls the entry of lymphocytes and antigens into lymph nodes

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