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

Nat Immunol. 2008 Jan;9(1):42-53. doi: 10.1038/ni1534. Epub 2007 Nov 25.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Endothelium, Lymphatic / immunology
  • Fingolimod Hydrochloride
  • Homeostasis
  • Inflammation / immunology
  • Integrin alpha4beta1 / immunology
  • Intercellular Adhesion Molecule-1 / immunology
  • Lymph Nodes / immunology
  • Lymphatic Vessels / immunology*
  • Lymphocyte Function-Associated Antigen-1 / immunology
  • Lysophospholipids / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Models, Immunological*
  • Propylene Glycols / pharmacology
  • Receptors, Lysosphingolipid / agonists
  • Receptors, Lysosphingolipid / antagonists & inhibitors
  • Receptors, Lysosphingolipid / immunology*
  • Signal Transduction
  • Sphingosine / analogs & derivatives*
  • Sphingosine / metabolism
  • Sphingosine / pharmacology
  • T-Lymphocytes / immunology*
  • Vascular Cell Adhesion Molecule-1 / immunology


  • Integrin alpha4beta1
  • Lymphocyte Function-Associated Antigen-1
  • Lysophospholipids
  • Propylene Glycols
  • Receptors, Lysosphingolipid
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • sphingosine 1-phosphate
  • Fingolimod Hydrochloride
  • Sphingosine

Associated data

  • GEO/GSE9237