Secrets and Lyase: New Roles of S1P Signaling in the Immune System

Immunology Interest Group Seminar Series Sphingosine 1-phosphate (S1P) signaling plays critical roles in the cardiovascular and immune systems. We have recently characterized a mouse that lacks the S1P transporter SPNS2. SPNS2-deficient mice have only a minor reduction in blood S1P and hence grossly normal vascular permeability, but a dramatic reduction in lymph S1P and hence severely disrupted lymphocyte trafficking. These mice have revealed unexpected functions of S1P gradients in positioning immune cells within lymphoid organs, as well as in supporting lymphocyte survival. Dr. Susan Schwab is Associate Professor at the Skirball Institute of Biomolecular Medicine in New York. She obtained her PhD with Nilabh Shastri at UC Berkeley and she did her post-doctoral fellowship with Jason Cyster at UCSF where she helped define the mechanisms by which the sphingosine 1-phosphate (S1P) receptor regulates lymphocyte egress from lymphoid organs, work that has contributed to now having a S1P lyase inhibitor in clinical trials for treatment of autoimmune disease. In her own lab, Susan has taken on the problem of how S1P gradients are established. Via the generation of a mouse expressing a novel reporter of signaling-available S1P and other elegant tools, her lab has recently identified two new players in the control of S1P distribution: the major facilitator superfamily transporter SPNS2 that facilitates lymphocyte exit from lymph nodes, and lipid phosphate phosphatase 3 which is essent...
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