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Alteration of Lymphocyte Trafficking by Sphingosine-1-Phosphate Receptor Agonists
Abstract
Blood lymphocyte numbers, essential for the development of efficient immune responses, are maintained by recirculation through secondary lymphoid organs. We show that lymphocyte trafficking is altered by the lysophospholipid sphingosine-1-phosphate (S1P) and by a phosphoryl metabolite of the immunosuppressive agent FTY720. Both species were high-affinity agonists of at least four of the five S1P receptors. These agonists produce lymphopenia in blood and thoracic duct lymph by sequestration of lymphocytes in lymph nodes, but not spleen. S1P receptor agonists induced emptying of lymphoid sinuses by retention of lymphocytes on the abluminal side of sinus-lining endothelium and inhibition of egress into lymph. Inhibition of lymphocyte recirculation by activation of S1P receptors may result in therapeutically useful immunosuppression.
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Citations
Cited by
Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1
Matloubian, M., Lo, C. G., Cinamon, G., Lesneski, M. J., Xu, Y., Brinkmann, V., Allende, M. L., Proia, R. L., & Cyster, J. G. (2004) · Nature · doi:10.1038/nature02284 · Cited by 2,581
Siddiqui, I., Schaeuble, K., Chennupati, V., Fuertes Marraco, S. A., Calderon-Copete, S., Pais Ferreira, D., Carmona, S. J., Scarpellino, L., Gfeller, D., Pradervand, S., et al. (2019) · Immunity · doi:10.1016/j.immuni.2018.12.021 · Cited by 1,679
Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis
Brinkmann, V., Billich, A., Baumruker, T., Heining, P., Schmouder, R., Francis, G., Aradhye, S., & Burtin, P. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3248 · Cited by 1,273
Chamorro, Á., Dirnagl, U., Urra, X., & Planas, A. M. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)00114-9 · Cited by 1,198
Regulation of Dendritic Cell Migration to the Draining Lymph Node
Martín-Fontecha, A., Sebastiani, S., Höpken, U. E., Uguccioni, M., Lipp, M., Lanzavecchia, A., & Sallusto, F. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030448 · Cited by 878
Metadata
- Authors
- Mandala, S., Hajdu, R., Bergstrom, J., Quackenbush, E., Xie, J., Milligan, J., Thornton, R., Shei, G.-J., Card, D., Keohane, C., Rosenbach, M., Hale, J., Lynch, C. L., Rupprecht, K., Parsons, W., & Rosen, H.
- Venue
- Science
- Published
- 2002-04-12
- Volume
- 296
- Issue
- 5566
- Pages
- 346-349
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2108813293
- Cited by
- 1,690
- References
- 0
- FWCI
- 25.92
- Type
- journal article
- Language
- en
- Open access
- closed
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- Mandala, S., Hajdu, R., Bergstrom, J., Quackenbush, E., Xie, J., Milligan, J., Thornton, R., Shei, G.-J., Card, D., Keohane, C., Rosenbach, M., Hale, J., Lynch, C. L., Rupprecht, K., Parsons, W., & Rosen, H. (2002). Alteration of Lymphocyte Trafficking by Sphingosine-1-Phosphate Receptor Agonists. Science. https://doi.org/10.1126/science.1070238
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