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Immune Regulation by Sphingosine 1-Phosphate and Its Receptors

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  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

It is well established that the lysophospholipid and signalling molecule sphingosine 1-phosphate (S1P) has many important functions in immune surveillance. S1P is produced from sphingosine by two distinct sphingosine kinases, SphK1 and SphK2, and acts as an intracellular messenger and as an extracellular ligand of five G protein-coupled cell surface receptors designated S1P1–S1P5. S1P not only regulates peripheral lymphocyte circulation, but also influences their differentiation, activation, infiltration, and local positioning. The therapeutic value of modulating S1P metabolism and S1P receptor function is currently tested in clinical trials and holds great promise for treatment of different autoimmune diseases. Despite its obvious contribution to immune regulation, the analysis of S1P is still challenging. A major obstacle is the difficulty to analyze S1P locally in tissues and within cells due to its high metabolic turnover and the limited resolution of current analytical techniques like liquid chromatography and mass spectrometry. This review focuses on recent advancements to our understanding how different sources of S1P contribute to immune function, and how changes in production, secretion, and degradation of S1P can influence immune responses.

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Abbreviations

S1P:

Sphingosine 1-phosphate

SGPL1:

S1P-lyase

SphK:

Sphingosine kinase

RBC:

Red blood cells

SA:

Serum albumin

HDL:

High-density lipoproteins

LPP:

Lipid phosphate phosphatase

PSA:

Passive systemic anaphylaxis

MZB:

Marginal zone B

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Acknowledgments

The authors were supported by the priority program 1267 “sphingolipids—signals and disease”, grant GR 1943/2-2 (to MHG.), and grant GR 1943/3-1 (to MHG.) from the German Research Foundation (DFG).

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  1. Molecular Cancer Research Centre (MKFZ), Charité University Medical School (CVK), Augustenburger Platz 1, Forum 4, 13353, Berlin, Germany

    Constantin Bode & Markus H. Gräler

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Correspondence to Markus H. Gräler.

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Bode, C., Gräler, M.H. Immune Regulation by Sphingosine 1-Phosphate and Its Receptors. Arch. Immunol. Ther. Exp. 60, 3–12 (2012). https://doi.org/10.1007/s00005-011-0159-5

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