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Type 4 sphingosine 1‐phosphate G protein‐coupled receptor (S1P 4 ) transduces S1P effects on T cell proliferation and cytokine secretion without signaling migration
Author(s) -
Wang Wengang,
Graeler Markus H.,
Goetzl Edward J.
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-3730fje
Subject(s) - microbiology and biotechnology , secretion , g protein coupled receptor , sphingosine , sphingosine 1 phosphate , biology , cytokine , chemokine , receptor , t cell , ccl5 , cd28 , signal transduction , immune system , il 2 receptor , immunology , biochemistry
Sphingosine 1‐phosphate (S1P) has diverse effects on T cells that are mediated by the predominant S1P 1 and S1P 4 G protein‐coupled receptors (GPCRs). S1P 4 is expressed principally by leukocytes, but little is known of its T cell effects in immunity. Two approaches were used to investigate S1P 4 signals in T cells. First, S1P 4 was introduced into D10G4.1 mouse Th2 cells and EL4.IL‐2 mouse T cells lacking endogenous S1P GPCRs. Second, mouse splenic CD4 T cells were treated with FTY720 to suppress S1P 1 and leave S1P 4 GPCRs as the only functionally relevant S1P receptor. Unlike S1P 1 , S1P 4 failed to transduce chemotactic responses of any of the S1P 4 ‐only T cells to S1P or the phyto‐S1P ligand selective for S1P 4 , or to suppress their chemotactic responses to chemokines. The S1P‐S1P 4 axis significantly inhibited T cell proliferation in each of the S1P 4 ‐only T cells activated by anti‐CD3 and anti‐CD28 MoAbs. Secretion of IL‐4 by S1P 4 ‐D10G4.1 cells, IL‐2 by S1P 4 ‐EL4.IL‐2, and IFN‐γ by FTY720‐treated CD4 T cells were significantly inhibited by S1P. In contrast, S1P enhanced secretion of IL‐10 by stimulated S1P 4 ‐D10G4.1 T cells. Thus, S1P 4 mediates immunosuppressive effects of S1P by inhibiting proliferation and secretion of effector cytokines, while enhancing secretion of the suppressive cytokine IL‐10.