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Suppression by natural CD4(+)CD25(+) regulatory T cells (Tregs) is one mechanism by which tolerance is maintained. However, the way in which Tregs mediate suppression is not well understood. Here, we show that secreted phospholipase A2 (sPLA2)-IID is selectively produced by Tregs. sPLA2-IID is a potent mediator of Treg function, because it strongly suppressed proliferation of CD4(+) and CD8(+) T cells in vitro and in vivo in a manner independent of its catalytic activity. Furthermore, sPLA2-IID promoted the differentiation of Tregs, presumably via attenuating signaling through the PI3K/Akt/mammalian target of rapamycin pathway. Importantly, administration of a sPLA2-IID-Fc fusion protein inhibited disease development in murine models of colitis and multiple sclerosis, suggesting that sPLA2-IID's immunosuppressive function might be exploited therapeutically.

Original publication

DOI

10.1073/pnas.0812569106

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

14/07/2009

Volume

106

Pages

11673 - 11678

Keywords

Adoptive Transfer, Animals, Cell Differentiation, Cell Proliferation, Colitis, DNA Primers, Flow Cytometry, Group II Phospholipases A2, Mice, Multiple Sclerosis, Recombinant Fusion Proteins, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, T-Lymphocytes, Regulatory