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Nat Immunol. 2015 Dec;16(12):1245-52. doi: 10.1038/ni.3296. Epub 2015 Oct 26.

A map of the distribution of sphingosine 1-phosphate in the spleen.

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Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA.
División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Distrito Federal, México.
Microscopy Core, Office of Collaborative Science, New York University Langone Medical Center, New York, New York, USA.


Despite the importance of signaling lipids, many questions remain about their function because few tools are available for charting lipid gradients in vivo. Here we generated a sphingosine 1-phosphate (S1P) reporter mouse and used this mouse to define the distribution of S1P in the spleen. Unexpectedly, the presence of blood did not serve as a predictor of the concentration of signaling-available S1P. Large areas of the red pulp had low concentrations of S1P, while S1P was sensed by cells inside the white pulp near the marginal sinus. The lipid phosphate phosphatase LPP3 maintained low S1P concentrations in the spleen and enabled efficient shuttling of marginal zone B cells. The exquisitely tight regulation of S1P availability might explain how a single lipid can simultaneously orchestrate the movements of many cells of the immune system.

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