Expression of the Sphingosine 1-Phosphate Receptor, S1P1, on T-cells Controls Thymic Emigration

• Published in: The Journal of biological chemistry 2004-04, Vol.279 (15), p.15396-15401
• Main Authors: Allende, Maria L., Dreier, Jennifer L., Mandala, Suzanne, Proia, Richard L.
• Format: Article
• Language: English
• Subjects: Animals; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - metabolism; Cell Movement; Chemotaxis; Dose-Response Relationship, Drug; Flow Cytometry; Gene Deletion; Immunohistochemistry; L-Selectin - chemistry; Ligands; Lymph Nodes - pathology; Mice; Mice, Knockout; Models, Genetic; Mutation; Receptors, G-Protein-Coupled - biosynthesis; Receptors, Lysophospholipid; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; T-Lymphocytes - cytology; T-Lymphocytes - metabolism; Thymus Gland - cytology; Thymus Gland - metabolism; Time Factors; Up-Regulation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M314291200

S1P1 is a widely distributed G protein-coupled receptor whose ligand, sphingosine 1-phosphate, is present in high concentrations in the blood. The sphingosine 1-phosphate receptor-signaling pathway is believed to have potent effects on cell trafficking in the immune system. To determine the precise role of the S1P1 receptor on T-cells, we established a T-cell-specific S1P1 knock-out mouse. The mutant mice showed a block in the egress of mature T-cells into the periphery. The expression of the S1P1 receptor was up-regulated in mature thymocytes, and its deletion altered the chemotactic responses of thymocytes to sphingosine 1-phosphate. The results indicated that the expression of the S1P1 receptor on T-cells controls their exit from the thymus and entry into the blood and, thus, has a central role in regulating the numbers of peripheral T-cells.