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Sphingosine 1‐phosphate and interleukin‐4 signaling requirements for peripheral conversion of naïve T cells to adaptive CD4+25+ regulatory T cells
Author(s) -
Marquez Christopher Phillip,
Huang MeiChuan,
Wang Wengang,
Goetzl Edward J.
Publication year - 2008
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/fasebj.22.1_supplement.848.1
Subject(s) - microbiology and biotechnology , chemokine , sphingosine 1 phosphate , cytokine , t cell , chemistry , chemotaxis , immune system , receptor , sphingosine , biology , immunology , biochemistry
Sphingosine 1‐phosphate (S1P) mediates the development and activities of regulatory T cells (Treg) of several types through its G protein‐coupled receptors. In T cells, type 1 (S1P 1 ) and type 4 (S1P 4 ) G protein‐coupled receptors are quantitatively predominant. As the dominant functional receptor, S1P 1 is responsible for the direct chemotactic response of CD4 T cells to S1P and inhibition of chemotactic responses to chemokines. S1P 1 also mediates part of the inhibitory effect of S1P on T cell proliferation in S1P 1 –transgenic (TG) mice. S1P 4 exerts immunosuppression by its effects on T cell proliferation and cytokine production. The local cytokine environment induces naïve CD4 + T helper cells (Th) to differentiate towards T helper 1 (Th1), Th2, Th17 and Treg phenotypes. This study explores the roles of physiological concentrations of S1P and interleukin‐4 (IL‐4) on naïve T cell differentiation in vitro into Treg and Th17 cells. We found that the absence of IL‐4 suppresses peripheral conversion of naïve splenic Th cells to Tregs and concurrently enhances their conversion to Th17 cells, which alters fundamental immune responses. Supported by Minority Access to Research Careers (MARC), Howard Hughes Medical Institute (HHMI), and RO‐1 grant HL31809 from the National Institutes of Health.