title: The endothelial protein PLVAP in lymphatics controls the entry of lymphocytes and antigens into lymph nodes.
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.
authors: MediCity Research Laboratory, University of Turku, Turku, Finland.
authors: Pia
authors: P
authors: Rantakari
authors: MediCity Research Laboratory, University of Turku, Turku, Finland.
authors: Kaisa
authors: K
authors: Auvinen
authors: MediCity Research Laboratory, University of Turku, Turku, Finland.
authors: Norma
authors: N
authors: Jäppinen
authors: MediCity Research Laboratory, University of Turku, Turku, Finland.
authors: Maria
authors: M
authors: Kapraali
authors: MediCity Research Laboratory, University of Turku, Turku, Finland.
authors: Joona
authors: J
authors: Valtonen
authors: MediCity Research Laboratory, University of Turku, Turku, Finland.
authors: Marika
authors: M
authors: Karikoski
authors: MediCity Research Laboratory, University of Turku, Turku, Finland.
authors: Heidi
authors: H
authors: Gerke
authors: MediCity Research Laboratory, University of Turku, Turku, Finland.
authors: Imtiaz
authors: I
authors: Iftakhar-E-Khuda
authors: MediCity Research Laboratory, University of Turku, Turku, Finland.
authors: Johannes
authors: J
authors: Keuschnigg
authors: WPI Immunology Frontier Research Center, Osaka University, Japan.
authors: Eiji
authors: E
authors: Umemoto
authors: Department of Anatomy, Kansai University of Health Sciences, Osaka, Japan.
authors: Kazuo
authors: K
authors: Tohya
authors: 1] MediCity Research Laboratory, University of Turku, Turku, Finland. [2] WPI Immunology Frontier Research Center, Osaka University, Japan.
authors: Masayuki
authors: M
authors: Miyasaka
authors: 1] MediCity Research Laboratory, University of Turku, Turku, Finland. [2] Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.
authors: Kati
authors: K
authors: Elima
authors: 1] MediCity Research Laboratory, University of Turku, Turku, Finland. [2] Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors: Sirpa
authors: S
authors: Jalkanen
authors: 1] MediCity Research Laboratory, University of Turku, Turku, Finland. [2] Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors: Marko
authors: M
authors: Salmi
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D051242:Caveolin 1 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology*; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D042601:Lymphatic Vessels / Q000166:cytology / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D057705:Transendothelial and Transepithelial Migration / Q000276:immunology
chemical_list: D000941:Antigens; D015703:Antigens, CD; D002352:Carrier Proteins; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D008565:Membrane Proteins; C486772:Plvap protein, mouse