Sphingosine-1-Phosphate: a Master Regulator of Lymphocyte Egress and Immunity
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Sphingosine-1-phosphate (S1P) is a central factor responsible for lymphocyte distribution in the body. S1P is able to control the integrity of various effector cell populations within many lymphoid tissues by directing lymphocyte egress. In this review, we give an overview of the generation and degradation of S1P in specific lymphoid microenvironments. Furthermore, we discuss, sometimes contradictory, the functions of the five S1P receptors on different cells in diverse tissues and give an idea of additional counteracting chemotactic signals for lymphocyte immigration and emigration. We focus special attention to recent discoveries of S1P-specific transporters, like spinster-homolog-2 and the active secretion of S1P by endothelial cells, erythrocytes and platelets. In addition, we describe the microanatomical structures as well as entry and egress routes into lymphoid organs which lymphocytes use for efficient trafficking. Finally, we give an overview of open questions regarding the regulation of lymphocyte homing from primary lymphoid organs to secondary lymphoid organs and back again.
KeywordsSphingosine-1-phosphate S1P receptors Lymphocyte egress Spinster-homolog-2
We thank Dr. Fritz Melchers (Max Planck Institute for Infection Biology, Berlin, Germany) and Dr. Alison Hobro (WPI-Immunology Frontier Research Center, Osaka, Japan) for critically reading the manuscript. This work was supported by Grants-in-Aid for Scientific Research (A) (25253070) and for Scientific Research on Innovative Areas (22113007), by the Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program) from the Ministry of Education, Science, Sports and Culture of Japan and by the grant from the International Human Frontier Science Program (RGY0077/2011) and by the Kishimoto Foundation, Osaka, Japan.
Conflict of interest
The authors declare no competing financial or commercial conflict of interest.
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