The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics

Levi G. Ledgerwood, Girdhari Lal, Nan Zhang, Alexandre Garin, Steven J. Esses, Florent Ginhoux, Miriam Merad, Helene Peche, Sergio A. Lira, Yaozhong Ding, Yu Yang, Xingxuan He, Edward H. Schuchman, Maria L. Allende, Jordi C. Ochando, Jonathan S. Bromberg

Research output: Contribution to journalArticlepeer-review

210 Scopus citations

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.

Original languageEnglish
Pages (from-to)42-53
Number of pages12
JournalNature Immunology
Volume9
Issue number1
DOIs
StatePublished - Jan 2008

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