Analysis of physiological roles of sphingosine-1-phosphate transporter, SPNS2

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Sphingosine-1-phoshphate (S1P), a bioactive lipid mediator, is intracellularly synthesized, released from the cells and recognized by S1P receptors (S1PR1-S1PR5). We had identified a novel S1P transporter, SPNS2. In order to reveal the physiological roles of SPNS2 in mammals, we analyzed SPNS2-knockout (KO) mice.S1P abundantly exists in plasma and plasma S1P is thought to originate from erythrocytes, activated platelets and endothelial cells. Vascular endothelial cells purified from SPNS2-KO mice are unable to release S1P, while S1P release from erythrocytes and platelets of SPNS2-KO mice is not changed. These results suggest that SPNS2 functions as the sole S1P transporter in endothelial cells. Furthermore, SPNS2-KO mice exhibited lymphopenia, while thymocytes are able to differentiate into mature cells and migrate towards S1P. These date indicate that S1P released by SPNS2 on endothelial cells is recognized by S1PR1 on matured thymocytes and enable thymic egress.