Article

The alliance of sphingosine-1-phosphate and its receptors in immunity

Laboratory of Immune Cell Signaling, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland 20892, USA.
Nature Reviews Immunology (Impact Factor: 33.84). 10/2008; 8(10):753-63. DOI: 10.1038/nri2400
Source: PubMed

ABSTRACT Sphingosine-1-phosphate (S1P) is a biologically active metabolite of plasma-membrane sphingolipids that is essential for immune-cell trafficking. Its concentration is increased in many inflammatory conditions, such as asthma and autoimmunity. Much of the immune function of S1P results from the engagement of a family of G-protein-coupled receptors (S1PR1-S1PR5). Recent findings on the role of S1P in immunosurveillance, the discovery of regulatory mechanisms in S1P-mediated immune-cell trafficking and new advances in understanding the mechanism by which S1P affects immune-cell function indicate that the alliance between S1P and its receptors has a fundamental role in immunity.

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    • "Sphingosine-1-phosphate (S1P) is a biologically active metabolite of plasma-membrane sphingolipids, which is essential for immune-cell trafficking (Rivera et al., 2008). It is elevated in many inflammatory diseases, such as asthma and autoimmunity (Rivera et al., 2008). In contrast to its weak effect on degranulation of murine mast cells, S1P potently induces degranulation of human mast cells (LAD2, skin mast cells and hCBMC) (Oskeritzian et al., 2008; Oskeritzian et al., 2010). "
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    European journal of pharmacology 07/2015; DOI:10.1016/j.ejphar.2015.07.017 · 2.68 Impact Factor
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    • "In both models, the mechanism for such suppression involved prevention of dendritic or Langerhans cell migration to the lymph nodes (Idzko et al., 2006; Reines et al., 2009) and in the dermatitis model, reduced antigen processing via S1P 2 receptor activation (Japtok et al., 2012). S1P has also been reported to exert anti-inflammatory roles by promoting the switch from the pro-inflammatory M1 to the anti-inflammatory M2 macrophage subtype (reviewed in (Rivera et al., 2008)). "
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    ABSTRACT: Sphingosine-1phosphate (S1P), platelet activating factor (PAF) and eicosanoids are bioactive lipid mediators abundantly produced by antigen-stimulated mast cells that exert their function mostly through specific cell surface receptors. Although it has long been recognized that some of these bioactive lipids are potent regulators of allergic diseases, their exact contributions to disease pathology have been obscured by the complexity of their mode of action and the regulation of their metabolism. Indeed, the effects of such lipids are usually mediated by multiple receptor subtypes that may differ in their signaling mechanisms and functions. In addition, their actions may be elicited by cell surface receptor-independent mechanisms. Furthermore, these lipids may be converted into metabolites that exhibit different functionalities, adding another layer of complexity to their overall biological responses. In some instances, a second wave of lipid mediator synthesis by both mast cell and non-mast cell sources may occur late during inflammation, bringing about additional roles in the altered environment. New evidence also suggests that bioactive lipids in the local environment can fine-tune mast cell maturation and phenotype, and thus their responsiveness. A better understanding of the subtleties of the spatiotemporal regulation of these lipid mediators, their receptors and functions may aid in the pursuit of pharmacological applications for allergy treatments. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmacology 05/2015; DOI:10.1016/j.ejphar.2015.02.058 · 2.68 Impact Factor
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    • "Recently, several chemokine-signaling axes have been shown to mediate Treg recruitment to tumors (Mailloux and Young, 2010; Nishikawa and Sakaguchi, 2010). In addition to G protein coupled receptor (GPCR) chemokine receptors, sphingosine-1 phosphate receptors (S1PR1–S1PR5) are also important regulators of immune cells, including T cells (Arnon et al., 2011; Rivera et al., 2008; Spiegel and Milstien, 2011), but their impact on tumor-associated T cells remains to be directly investigated. "
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