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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1314-1322. Prepublished online as a Blood First Edition Paper on May 3, 2005; DOI 10.1182/blood-2004-09-3687. This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 2004-09-3687v1 106/4/1314    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Halin, C. Articles by von Andrian, U. H. Search for Related Content PubMed PubMed Citation Articles by Halin, C. Articles by von Andrian, U. H. Related Collections Immunobiology Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY The S1P-analog FTY720 differentially modulates T-cell homing via HEV: T-cell–expressed S1P1 amplifies integrin activation in peripheral lymph nodes but not in Peyer patches Cornelia Halin, M. Lucila Scimone, Roberto Bonasio, Jean-Marc Gauguet, Thorsten R. Mempel, Elizabeth Quackenbush, Richard L. Proia, Suzanne Mandala, and Ulrich H. von Andrian From the CBR Institute for Biomedical Research and the Department of Pathology, Harvard Medical School, Boston, MA; the Department of Immunology and Rheumatology, Merck Research Laboratories, Rahway, NJ; and the Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. Sphingosine-1-phosphate (S1P) and its receptor S1P1 control T-cell egress from thymus and secondary lymphoid organs (SLOs). To further define the role of S1P1 in lymphocyte trafficking, we performed adoptive transfer experiments and intravital microscopy (IVM) using both S1P1–/– lymphocytes and recipient wild-type (WT) mice treated with FTY720, an immunosuppressant that downmodulates S1P receptors. S1P1 deficiency and FTY720 caused rapid disappearance of T cells from blood, prolonged retention in SLOs, and accumulation in bone marrow, but did not alter interstitial T-cell motility in peripheral lymph nodes (PLNs) as assessed by multiphoton IVM. However, S1P1–/– lymphocytes displayed reduced short-term homing to PLNs due to attenuated integrin-mediated firm arrest in high endothelial venules (HEVs). By contrast, S1P1–/– T cells homed normally to Peyer patches (PPs), whereas S1P1–/– B cells had a marked defect in homing to PPs and arrested poorly in PP HEVs. Therefore, S1P1 not only controls lymphocyte egress from SLOs, but also facilitates in a tissue- and subset-specific fashion integrin activation during homing. Interestingly, FTY720 treatment enhanced accumulation of both S1P1 sufficient and S1P1–/– T cells in PPs by enhancing integrin-mediated arrest in HEVs. Thus, FTY720 exerts unique effects on T-cell traffic in PPs that are independent of T-cell–expressed S1P1. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Kohno and Y. Igarashi Attenuation of cell motility observed with high doses of sphingosine 1-phosphate or phosphorylated FTY720 involves RGS2 through its interactions with the receptor S1P. Genes Cells, July 1, 2008; 13(7): 747 - 757. [Abstract] [Full Text] [PDF] H. Zheng, B. Jin, S. E. Henrickson, A. S. Perelson, U. H. von Andrian, and A. K. Chakraborty How Antigen Quantity and Quality Determine T-Cell Decisions in Lymphoid Tissue Mol. 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[Abstract] [Full Text] [PDF] M. L. Scimone, I. Aifantis, I. Apostolou, H. von Boehmer, and U. H. von Andrian A multistep adhesion cascade for lymphoid progenitor cell homing to the thymus PNAS, May 2, 2006; 103(18): 7006 - 7011. [Abstract] [Full Text] [PDF] O. Pabst, H. Herbrand, S. Willenzon, T. Worbs, A. Schippers, W. Muller, G. Bernhardt, and R. Forster Enhanced FTY720-Mediated Lymphocyte Homing Requires G{alpha}i Signaling and Depends on beta2 and beta7 Integrin J. Immunol., February 1, 2006; 176(3): 1474 - 1480. [Abstract] [Full Text] [PDF] I. I. Singer, M. Tian, L. A. Wickham, J. Lin, S. S. Matheravidathu, M. J. Forrest, S. Mandala, and E. J. Quackenbush Sphingosine-1-Phosphate Agonists Increase Macrophage Homing, Lymphocyte Contacts, and Endothelial Junctional Complex Formation in Murine Lymph Nodes J. Immunol., December 1, 2005; 175(11): 7151 - 7161. [Abstract] [Full Text] [PDF] P. Bandhuvula, Y. Y. Tam, B. Oskouian, and J. D. 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