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Nat Immunol. 2009 Jul;10(7):769-77. doi: 10.1038/ni.1743. Epub 2009 May 31.

The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR.

Author information

1
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Abstract

Regulatory T cells (T(reg) cells) are critically involved in maintaining immunological tolerance, but this potent suppression must be 'quenched' to allow the generation of adaptive immune responses. Here we report that sphingosine 1-phosphate (S1P) receptor type 1 (S1P1) delivers an intrinsic negative signal to restrain the thymic generation, peripheral maintenance and suppressive activity of T(reg) cells. Combining loss- and gain-of-function genetic approaches, we found that S1P1 blocked the differentiation of thymic T(reg) precursors and function of mature T(reg) cells and affected T(reg) cell-mediated immune tolerance. S1P1 induced selective activation of the Akt-mTOR kinase pathway to impede the development and function of T(reg) cells. Dynamic regulation of S1P1 contributed to lymphocyte priming and immune homeostasis. Thus, by antagonizing T(reg) cell-mediated immune suppression, the lipid-activated S1P1-Akt-mTOR pathway orchestrates adaptive immune responses.

PMID:
19483717
PMCID:
PMC2732340
DOI:
10.1038/ni.1743
[Indexed for MEDLINE]
Free PMC Article

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