title: Dendritic cells control lymphocyte entry to lymph nodes through high endothelial venules.
abstract: While patrolling the body in search of foreign antigens, naive lymphocytes continuously circulate from the blood, through the lymph nodes, into the lymphatic vessels and back to the blood. This process, called lymphocyte recirculation, provides the body with effective immune surveillance for foreign invaders and for alterations to the body's own cells. However, the mechanisms that regulate lymphocyte recirculation during homeostasis remain incompletely characterized. Here we show that dendritic cells (DCs), which are well known for their role in antigen presentation to T lymphocytes, control the entry of naive lymphocytes to lymph nodes by modulating the phenotype of high endothelial venules (HEVs), which are blood vessels specialized in lymphocyte recruitment. We found that in vivo depletion of CD11c(+) DCs in adult mice over a 1-week period induces a reduction in the size and cellularity of the peripheral and mucosal lymph nodes. In the absence of DCs, the mature adult HEV phenotype reverts to an immature neonatal phenotype, and HEV-mediated lymphocyte recruitment to lymph nodes is inhibited. Co-culture experiments showed that the effect of DCs on HEV endothelial cells is direct and requires lymphotoxin-β-receptor-dependent signalling. DCs express lymphotoxin, and DC-derived lymphotoxin is important for lymphocyte homing to lymph nodes in vivo. Together, our results reveal a previously unsuspected role for DCs in the regulation of lymphocyte recirculation during immune surveillance.
authors.affiliation: CNRS, Institut de Pharmacologie et de Biologie Structurale, 205 route de Narbonne, F-31077 Toulouse, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Moussion
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Girard
mesh_terms: D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology*; D006706:Homeostasis / Q000276:immunology; D007157:Immunologic Surveillance / Q000276:immunology; D036904:Leukocyte Rolling; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology; D008208:Lymphatic System / Q000166:cytology* / Q000276:immunology*; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D016201:Receptors, Lymphocyte Homing
chemical_list: D039521:CD11c Antigen; D008233:Lymphotoxin-alpha; D016201:Receptors, Lymphocyte Homing
references.citation: Nat Rev Immunol. 2003 Nov;3(11):867-78
references.pmid: 14668803
references.citation: J Exp Med. 2009 Oct 26;206(11):2339-49
references.pmid: 19808255
references.citation: Nature. 1998 Mar 19;392(6673):245-52
references.pmid: 9521319
references.citation: Nat Immunol. 2008 Apr;9(4):388-95
references.pmid: 18311142
references.citation: J Immunol Methods. 1999 Feb 1;223(1):77-92
references.pmid: 10037236
references.citation: PLoS One. 2008 Oct 06;3(10):e3331
references.pmid: 18836528
references.citation: Mol Cell Biol. 2002 Dec;22(24):8626-34
references.pmid: 12446781
references.citation: J Immunol. 2005 Nov 15;175(10):6428-35
references.pmid: 16272295
references.citation: Science. 1996 Apr 5;272(5258):60-6
references.pmid: 8600538
references.citation: Nature. 2004 Jan 8;427(6970):154-9
references.pmid: 14712275
references.citation: Nature. 1987 Jan 15-21;325(6101):253-7
references.pmid: 3543687
references.citation: Immunity. 2002 Aug;17(2):211-20
references.pmid: 12196292
references.citation: J Immunol. 2011 Jul 15;187(2):828-34
references.pmid: 21666055
references.citation: Annu Rev Immunol. 2004;22:129-56
references.pmid: 15032576
references.citation: Eur J Immunol. 1998 Oct;28(10):3040-7
references.pmid: 9808172
references.citation: J Cell Biol. 1991 Oct;115(1):85-95
references.pmid: 1918141
references.citation: Microcirculation. 1996 Sep;3(3):287-300
references.pmid: 8930886
references.citation: Blood. 2008 Dec 15;112(13):5016-25
references.pmid: 18802011
references.citation: Nature. 2000 Jul 20;406(6793):309-14
references.pmid: 10917533
references.citation: Nat Rev Immunol. 2004 May;4(5):360-70
references.pmid: 15122201
references.citation: J Immunol. 2006 Sep 1;177(5):3369-79
references.pmid: 16920978
references.citation: Cancer Res. 2005 Dec 15;65(24):11639-48
references.pmid: 16357175
references.citation: Nat Immunol. 2005 Nov;6(11):1096-104
references.pmid: 16227985
references.citation: Nat Immunol. 2005 Nov;6(11):1105-13
references.pmid: 16227986
references.citation: Nat Immunol. 2006 Dec;7(12):1299-308
references.pmid: 17086187
references.citation: Blood. 2007 Jan 15;109(2):584-94
references.pmid: 17003378
references.citation: J Exp Med. 2003 Sep 1;198(5):715-24
references.pmid: 12953093
references.citation: Blood. 2004 Jun 1;103(11):4164-72
references.pmid: 14976058
references.citation: Cell. 1996 Aug 23;86(4):643-53
references.pmid: 8752218
references.citation: Immunity. 2005 Nov;23(5):539-50
references.pmid: 16286021
references.citation: J Immunol. 1993 Dec 15;151(12):6769-76
references.pmid: 7505014
references.citation: J Exp Med. 2006 Aug 7;203(8):1903-13
references.pmid: 16831898
references.citation: Eur J Immunol. 1997 Oct;27(10):2600-9
references.pmid: 9368616
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11019-24
references.pmid: 8855301
references.citation: Immunol Today. 1995 Sep;16(9):449-57
references.pmid: 7546210
references.citation: J Cell Biol. 1988 Nov;107(5):1853-62
references.pmid: 2460470
references.citation: Eur J Immunol. 1983 Aug;13(8):663-9
references.pmid: 6884423