Cutting edge: regulation of T cell trafficking and primary immune responses by sphingosine 1-phosphate receptor 1.
Signaling by sphingosine 1-phosphate (S1P) through its receptor S1P(1) has recently been shown to promote thymocyte egress. In the periphery, S1P(1) is expressed on naive T cells but lost upon T cell activation. To determine the significance of S1P(1) down-regulation and function of S1P(1) in peripheral T cells, we developed transgenic mice that constitutively express S1P(1) in T cells. Mature T cells from these mice exhibited enhanced chemotactic response toward S1P, and preferentially distributed to the blood rather than secondary lymphoid organs. S1P(1)-transgenic mice showed significant delay in the onset of experimental autoimmune encephalomyelitis, and had defective contact hypersensitivity reaction and local Ag-induced responses. These impairments were associated with reduced numbers of Ag-activated T cells in the draining lymph nodes. Our studies demonstrate that S1P(1) signaling affects systemic trafficking of peripheral T cells and immune responses and highlight that levels of S1P(1) expression represent an important mechanism of immune regulation.
Chi
Hongbo
H
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Flavell
Richard A
RA
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D049349:Receptors, Lysosphingolipid