Article abstract
Nature Immunology 9, 42 - 53 (2008)
Published online: 25 November 2007 | doi:10.1038/ni1534
The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics
Levi G Ledgerwood1,8, Girdhari Lal1,8, Nan Zhang1, Alexandre Garin2, Steven J Esses1, Florent Ginhoux1, Miriam Merad1, Helene Peche2, Sergio A Lira2, Yaozhong Ding1,2,3,4, Yu Yang1,3,4, Xingxuan He5, Edward H Schuchman5, Maria L Allende6, Jordi C Ochando1,7,8 & Jonathan S Bromberg1,2,3,4
Abstract
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.
- Immunobiology Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
- Department of Surgery, Mount Sinai School of Medicine, New York, New York 10029, USA.
- Recanati/Miller Transplantation Institute, Mount Sinai School of Medicine, New York, New York 10029, USA.
- Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA.
- Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
- Present address: Unidad de Immunología de Trasplantes, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28220 Madrid, Spain.
- These authors contributed equally to this work.
Correspondence to: Jonathan S Bromberg1,2,3,4 e-mail: Jon.Bromberg@mountsinai.org
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