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Nat Immunol. 2015 Apr;16(4):386-96. doi: 10.1038/ni.3101. Epub 2015 Feb 9.

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

Author information

1
MediCity Research Laboratory, University of Turku, Turku, Finland.
2
WPI Immunology Frontier Research Center, Osaka University, Japan.
3
Department of Anatomy, Kansai University of Health Sciences, Osaka, Japan.
4
1] MediCity Research Laboratory, University of Turku, Turku, Finland. [2] WPI Immunology Frontier Research Center, Osaka University, Japan.
5
1] MediCity Research Laboratory, University of Turku, Turku, Finland. [2] Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.
6
1] MediCity Research Laboratory, University of Turku, Turku, Finland. [2] Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.

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.

Comment in

PMID:
25665101
DOI:
10.1038/ni.3101
[Indexed for MEDLINE]

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