The alliance of sphingosine-1-phosphate and its receptors in immunity

Abstract

Recent research has shown that the interaction of sphingosine-1-phosphate with its receptors (S1PR1–S1PR5) has an essential role in regulating immune responses, not only through the control of immune-cell trafficking but also through effects on immune-cell function. Understanding these effects holds promise for the use of S1PR ligands as immunomodulatory therapeutics. Sphingosine-1-phosphate (S1P) is a biologically active metabolite of plasma-membrane sphingolipids that is essential for immune-cell trafficking. Its concentration is increased in many inflammatory conditions, such as asthma and autoimmunity. Much of the immune function of S1P results from the engagement of a family of G-protein-coupled receptors (S1PR1–S1PR5). Recent findings on the role of S1P in immunosurveillance, the discovery of regulatory mechanisms in S1P-mediated immune-cell trafficking and new advances in understanding the mechanism by which S1P affects immune-cell function indicate that the alliance between S1P and its receptors has a fundamental role in immunity.