Lipid phosphate phosphatase 3 maintains low thymic sphingosine-1-phosphate and enables efficient thymic egress (149.8)

Abstract

Abstract The signaling lipid sphingosine-1-phosphate (S1P) stabilizes the vasculature, directs lymphocyte circulation, and shapes inflammatory responses. However, little is known about how S1P distribution is controlled in vivo, and it is not clear how a ubiquitously made lipid functions as a signal that requires precise spatial and temporal control. Here we have found that lipid phosphate phosphatase 3 (LPP3) maintains low thymic S1P and efficient egress of mature T cells from the thymus into circulation. Although five additional S1P-degrading enzymes are expressed in the thymus, they cannot compensate for the loss of LPP3. Moreover, conditional deletion of LPP3 in either epithelial cells or endothelial cells is sufficient to increase thymic S1P. These results suggest that S1P generation and destruction are tightly regulated, and LPP3 is essential to establish the balance.