Figure 3: S1P gradient attracts lymphocytes and promotes egress of lymphocytes into the blood. A) sphingosine 1 phosphate (S1P) level in lymphoid tissues is low compared with the blood, this attracts lymphocytes and promotes S1PR1-dependent egress into the blood. S1P is bound to albumin (Alb) and high-density lipoprotein (HDL). S1PR1 maintains endothelium barrier function by promoting cellcell interactions. B) When T cells are ready to exit the thymus and enter the blood; S1PR1 is re-expressed respond to the chemotactic effect of high S1P levels. In the blood, S1P downregulates S1PR1. Lymphocyte egress into lymphatic vessel also requires S1PR1. Increased lymphoid tissue S1P, by SPL inhibition, or in the presence of S1PR1 modulators such as FTY720, blocks egress of lymphocytes by disruption of the S1P gradient or desensitization of S1PR1 on T cells, respectively.