Sphingosine-1-phosphate signaling as a therapeutic target

Eirini Giannoudaki, David J Swan, John A Kirby, Simi AliApplied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UKAbstract: Sphingosine 1-phosphate (S1P) is a small bioactive lipid molecule that is involved in several processes both intracellularly and extracellularly. It acts intracellularly to promote the survival and growth of the cell, through its interaction with molecules in different compartments of the cell. Extracellularly, it can exist at high concentrations in the blood plasma and lymph, further down inside the tissue. This causes an S1P gradient important for cell migration. S1P signals through five G protein-coupled receptors, S1PR1–S1PR5, whose expression varies in different types of cells and tissue. S1P signaling can be involved in physiological and pathophysiological conditions of the cardiovascular, nervous, and immune systems and diseases such as ischemia/reperfusion injury, autoimmunity, and cancer. In this review, we discuss this involvement and how it can be used to discover novel therapeutic targets.Keywords: S1P, CD69, T-cell activation, lymph node, recirculation