The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
FTY720: Sphingosine 1-Phosphate Receptor-1 in the Control of Lymphocyte Egress and Endothelial Barrier Function
Open accessAbstract
The novel immunomodulator FTY720 is effective in experimental models of transplantation and autoimmunity, and is currently undergoing Phase III clinical trials for prevention of kidney graft rejection. In contrast to conventional immunosuppressants, FTY720 does not impair T- and B-cell activation, proliferation and effector function, but interferes with cell traffic between lymphoid organs and blood. The molecular basis for the mode of action of the drug has only recently been established. FTY720, after phosphorylation, acts as a high-affinity agonist at the G protein-coupled sphingosine 1-phosphate receptor-1 (S1P(1)) on thymocytes and lymphocytes, thereby inducing aberrant internalization of the receptor. This renders the cells unresponsive to the serum lipid sphingosine 1-phosphate (S1P), depriving them from an obligatory signal to egress from lymphoid organs. As a consequence, lymphocytes are unable to recirculate to peripheral inflammatory tissues and graft sites but remain functional in the lymphoid compartment. In addition to the effects on lymphocyte recirculation, the drug acts on endothelial cells and preserves vascular integrity by enhancing adherens junction assembly and endothelial barrier function. The available data establish S1P(1) as a key target for FTY720, and further point to therapeutically relevant effects of the drug on lymphocytes and vascular endothelium.
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Cites
Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
Sallusto, F., Lenig, D., Förster, R., Lipp, M., & Lanzavecchia, A. (1999) · Nature · doi:10.1038/44385 · Cited by 5,846
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
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Cited by
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
Self-citationCD69 acts downstream of interferon-α/β to inhibit S1P1 and lymphocyte egress from lymphoid organs
Shiow, L. R., Rosen, D. B., Brdičková, N., Xu, Y., An, J., Lanier, L. L., Cyster, J. G., & Matloubian, M. (2006) · Nature · doi:10.1038/nature04606 · Cited by 1,189
Self-citationChemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs
Cyster, J. G. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115628 · Cited by 856
Self-citationMechanism of Action of Oral Fingolimod (FTY720) in Multiple Sclerosis
Chun, J., & Hartung, H.-P. (2010) · Clinical Neuropharmacology · doi:10.1097/wnf.0b013e3181cbf825 · Cited by 796
Lymphocyte Sequestration Through S1P Lyase Inhibition and Disruption of S1P Gradients
Schwab, S. R., Pereira, J. P., Matloubian, M., Xu, Y., Huang, Y., & Cyster, J. G. (2005) · Science · doi:10.1126/science.1113640 · Cited by 787
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Metadata
- Authors
- Brinkmann, V., Cyster, J. G., & Hla, T.
- Venue
- American Journal of Transplantation
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 4
- Issue
- 7
- Pages
- 1019-1025
- ISSN
- 1600-6135 (ISSN-L)
- OpenAlex
- W2078775078
- Cited by
- 478
- References
- 2
- FWCI
- 12.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Brinkmann, V., Cyster, J. G., & Hla, T. (2004). FTY720: Sphingosine 1-Phosphate Receptor-1 in the Control of Lymphocyte Egress and Endothelial Barrier Function. American Journal of Transplantation. https://doi.org/10.1111/j.1600-6143.2004.00476.x
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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