The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics.
Although much is known about the migration of T cells from blood to lymph nodes, less is known about the mechanisms regulating the migration of T cells from tissues into lymph nodes through afferent lymphatics. Here we investigated T cell egress from nonlymphoid tissues into afferent lymph in vivo and developed an experimental model to recapitulate this process in vitro. Agonism of sphingosine 1-phosphate receptor 1 inhibited the entry of tissue T cells into afferent lymphatics in homeostatic and inflammatory conditions and caused the arrest, mediated at least partially by interactions of the integrin LFA-1 with its ligand ICAM-1 and of the integrin VLA-4 with its ligand VCAM-1, of polarized T cells at the basal surface of lymphatic but not blood vessel endothelium. Thus, the increased sphingosine 1-phosphate present in inflamed peripheral tissues may induce T cell retention and suppress T cell egress.
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
Levi G
LG
Ledgerwood
Girdhari
G
Lal
Nan
N
Zhang
Alexandre
A
Garin
Steven J
SJ
Esses
Florent
F
Ginhoux
Miriam
M
Merad
Helene
H
Peche
Sergio A
SA
Lira
Yaozhong
Y
Ding
Yu
Y
Yang
Xingxuan
X
He
Edward H
EH
Schuchman
Maria L
ML
Allende
Jordi C
JC
Ochando
Jonathan S
JS
Bromberg
D000818:Animals; D002465:Cell Movement; D004729:Endothelium, Lymphatic / Q000276:immunology; D000068876:Fingolimod Hydrochloride; D006706:Homeostasis; D007249:Inflammation / Q000276:immunology; D039041:Integrin alpha4beta1 / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D042601:Lymphatic Vessels / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D011409:Propylene Glycols / Q000494:pharmacology; D049349:Receptors, Lysosphingolipid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology*; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D039041:Integrin alpha4beta1; D016169:Lymphocyte Function-Associated Antigen-1; D008246:Lysophospholipids; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C060506:sphingosine 1-phosphate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine