[Regulation of immunity by sphingosine 1-phosphate and its G protein-coupled receptors--review].
Sphingosine 1-phosphate (S1P) is an important biologically active lysophospholipid that transmits signals through a family of G-protein-coupled receptors (GPCRs) to regulate the vital functions of several types of immune cells. The S1P GPCRs suppress both generation of specialized functional cytokines, such as IFN-gamma and IL-4, and proliferation of T-cells. Although S1P is chemotactic to T cells, B cells, dendritic cells, and natural killer cells, the major effect of S1P on the immune system is the regulation of lymphocyte recirculation and tissue distribution by S1P and S1P1. Chemotactic response of CD4+CD25+ regulatory T cells to S1P is reduced, but its optimal suppressive activities require S1P. FTY720, a new class of immunomodulator, is rapidly phosphorylated by sphingosine kinase 2 in vivo to form the biologically active phosphorylated-FTY720 (FTY720-P), which closely resembles S1P. The FTY720-P is a true agonist for S1P1, S1P3, S1P4, and S1P5, it affects the tissue distribution and functional activity of T cells, B cells, dendritic cells and regulatory T cells. FTY720 were demonstrated to be a hypotoxic, great effective and reversible immunosuppressive efficacy to prevent allograft rejection and treat some autoimmune diseases. In this article, the synthesis and metabolism of S1P, the expression of S1P GPCRs in immune cells, the effect of S1P on immune cells, the drugs targeted to S1P GPCRs and their clinical implications are reviewed.
Zhu
Hai-Yan
HY
Department of Hematology, The General Hospital of PLA, Beijing 100853, China.
Da
Wan-Ming
WM
D000068876:Fingolimod Hydrochloride; D006801:Humans; D056747:Immunomodulation / Q000502:physiology*; D008246:Lysophospholipids / Q000276:immunology* / Q000502:physiology; D011409:Propylene Glycols / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000276:immunology* / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism / Q000502:physiology
D008246:Lysophospholipids; D011409:Propylene Glycols; D043562:Receptors, G-Protein-Coupled; C060506:sphingosine 1-phosphate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine