Nature Immunology 6, 1228 - 1235 (2005)
Published online: 6 November 2005; | doi:10.1038/ni1269
Sphingosine 1-phosphate type 1 receptor agonism inhibits transendothelial migration of medullary T cells to lymphatic sinusesSindy H Wei1, 5, Hugh Rosen2, 5, Melanie P Matheu1, M Germana Sanna2, Sheng-Kai Wang3, Euijung Jo2, Chi-Huey Wong3, Ian Parker4
& Michael D Cahalan11
Department of Physiology and Biophysics and Center for Immunology, University of California, Irvine, California 92697-4561, USA. 2
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA. 3
Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA. 4
Department of Neurobiology and Behavior, University of California, Irvine, California 92697-4550, USA. 5
These authors contributed equally to this work.
Correspondence should be addressed to Michael D Cahalan mcahalan@uci.edu or Hugh Rosen hrosen@scripps.edu Sphingosine 1-phosphate type 1 (S1P1) receptor agonists cause sequestration of lymphocytes in secondary lymphoid organs by a mechanism that is not well understood. One hypothesis proposes that agonists act as 'functional antagonists' by binding and internalizing S1P1 receptors on lymphocytes; a second hypothesis proposes instead that S1P1 agonists act on endothelial cells to prevent lymphocyte egress from lymph nodes. Here, two-photon imaging of living T cells in explanted lymph nodes after treatment with S1P1 agonists or antagonists has provided insight into the mechanism by which S1P1 agonists function. The selective S1P1 agonist SEW2871 caused reversible slowing and 'log-jamming' of T cells between filled medullary cords and empty sinuses, whereas motility was unaltered in diffuse cortex. Removal or antagonist competition of SEW2871 permitted recovery of T cell motility in the parenchyma of the medulla and resumption of migration across the stromal endothelial barrier, leading to refilling of sinuses. Our results provide visualization of transendothelial migration of T cells into lymphatic sinuses and suggest that S1P1 agonists act mainly on endothelial cell S1P1 receptors to inhibit lymphocyte migration.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
