Expression of the sphingosine 1-phosphate receptor, S1P1, on T-cells controls thymic emigration.
S1P(1) 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 S1P(1) receptor on T-cells, we established a T-cell-specific S1P(1) knock-out mouse. The mutant mice showed a block in the egress of mature T-cells into the periphery. The expression of the S1P(1) 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 S1P(1) 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.
Allende
Maria L
ML
Genetics of Development and Disease Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1821, USA.
Dreier
Jennifer L
JL
Mandala
Suzanne
S
Proia
Richard L
RL
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002465:Cell Movement; D002633:Chemotaxis; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D017353:Gene Deletion; D007150:Immunohistochemistry; D019041:L-Selectin / Q000737:chemistry; D008024:Ligands; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D009154:Mutation; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*; D049312:Receptors, Lysophospholipid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D019041:L-Selectin