The role of lipid phosphate phosphatase 1 in lymphocyte egress from lymphoid organs (173.39)

Abstract The signaling lipid sphingosine 1-phosphate (S1P) regulates vascular permeability, lymphocyte trafficking, and inflammation. The concentration of S1P is high in blood and lymph compared to lymphoid organs, and this difference guides lymphocyte exit from lymphoid organs into circulation. 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. Lipid phosphate phosphatase 3 (LPP3) is essential to maintain low S1P in the thymus, and we asked whether its homolog LPP1 cooperates with LPP3 to regulate lymphoid S1P. Measurements of Lpp1 messenger RNA indicate that, like Lpp3, Lpp1 is highly expressed by thymic endothelial and epithelial cells, and lymph node (LN) lymphatic endothelial, blood endothelial, and fibroblastic reticular cells. Using mice deficient in LPP1, we have found that LPP1 is not required to maintain low S1P in thymus or LN or to enable efficient lymphocyte egress. Mice doubly deficient in LPP1 and LPP3 preliminarily have a small accumulation of mature thymocytes and minor reduction in the number of T cells in lymph compared to mice deficient in LPP3 alone, suggestive of an egress defect. Further work will test the hypothesis that LPP1 and LPP3 work together to maintain low lymphoid organ S1P and efficient lymphocyte circulation.