The role of S1P-S1PR1 axis in T cell trafficking. S1P is maintained at low concentration in the thymus and lymphoid organs and is in high concentration in blood, binding to ApoM in HDL particles. S1PR1 expression in T cells is downregulated in blood, and T cells are shifted into lymphoid organs with CCR7 signaling. CD69 forms a complex with S1PR1 and downregulates S1PR1 to promote retention in activated T cells. Because Dnm2 enables continuous S1PR1 signaling in lymphocytes, effector T cells can sense low S1P condition and egress from lymphoid organs. ApoM: apolipoprotein M; HDL: high-density lipoprotein; CCR7: CC-chemokine receptor 7; TCR: T cell receptor; Dnm2: dynamin 2.