Expression and function of the type 1 sphingosine 1-phosphate receptor (S1P1-R) in immunity

Sphingosine 1-phosphate (S1P) is present in blood and lymph at concentrations sufficient to engage a group of five G protein-coupled receptors (Rs), that specifically bind S I P as their preferred ligand. Naive lymphocytes express mainly S1P(1)- and S1P(4)-Rs. Both S1P-Rs are rapidly down-regulated after T and B cell activation. Naive lymphocytes migrate to SIP, which is mediated by the S1P(1)-R and important for maintaining thymocyte exitation and lymphocyte re-circulation in vivo. The immunosuppressant FTY720 down-regulates S1P(1) which consequently prevents thymocyte exitation and lymphocyte egress from lymph nodes to lymphatics and into the bloodstream. T cell-targeted transgenic (Tg) S1P(1)-R expression in mice, that prevents down-regulation of endogenous SIP, alters lymphocyte trafficking and induces immunosuppression.