The adaptive immune system relies on constant circulation of lymphocytes between lymphoid organs and other tissues of the body. After maturation, lymphocytes leave the bone marrow or thymus, enter the circulation, and travel via the blood and the lymphatic system, surveying for antigens they recognize.

In the secondary lymphoid organs, which include lymph nodes, Peyer's patches, and the spleen, naïve lymphocytes encounter antigen-presenting cells and may be activated. Once activated, T cells must leave the lymph node to reach target tissues, whereas B cells can secrete antibodies without leaving the secondary lymphoid organs.

Circulation of lymphocytes between blood, lymphatic system, and non-lymphoid tissues is tightly regulated, and it has recently been shown that the lysophospholipid sphingosine-1-phosphate (S1P) plays a central role in lymphocyte trafficking.

Sphingosine-1-phospate (S1P) is a phospholipid released by platelets, mast and other cells. It is now known that S1P stimulates at least five different G-protein coupled receptors (GPCRs): S1P1, S1P2, S1P3, S1P4, and S1P5. Activation of these GPCRs mediates a complex variety of biological responses, such as lymphocyte migration, endothelial cell proliferation, blood vessel constriction, heart rate modulation and others. The concentration of S1P is low within the lymph node interior, but very high in the adjacent draining lymphatic vessels. These two compartments are separated by lymphatic endothelium.

Lymphocytes are able to sense a concentration gradient of S1P and migrate towards the higher S1P concentration. The migration of lymphocytes out of secondary lymphoid organs is dependent on the S1P1 receptor.


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