| Despite the importance of signaling lipids, analysis of lipids presents unique challenges, and little is known about their distribution in vivo. The signaling lipid sphingosine 1-phosphate (S1P) regulates diverse aspects of immune cell trafficking and function, but many processes remain poorly understood because the location of signaling-available S1P is not well-defined. We have developed an S1P reporter mouse, which enables mapping of S1P gradients in tissues. We have used this mouse to map S1P in the spleen and to address how the S1P degrading enzyme lipid phosphate phosphatase 3(LPP3) shapes these gradients. We have found that large areas of the blood-rich red pulp, generally thought to be S1P-high, in fact have low concentrations of signaling-available S1P. LPP3 is required to maintain low red pulp S1P. Furthermore, we have found that there is a sharp S1P differential between the B cell follicles and the marginal zone. LPP3 is required to maintain this boundary and enable efficient marginal zone B cell shuttling between the white pulp and marginal zone. The exquisitely tight regulation of S1P levels may explain how S1P can simultaneously orchestrate many types of immune cell movement. |
