Secretory phospholipase A2-IID is an effector molecule of CD4⁺CD25⁺ regulatory T cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 28; pp. 11673 - 11678
• Main Authors: von Allmen, Caroline E, Schmitz, Nicole, Bauer, Monika, Hinton, Heather J, Kurrer, Michael O, Buser, Regula B, Gwerder, Myriam, Muntwiler, Simone, Sparwasser, Tim, Beerli, Roger R, Bachmann, Martin F
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 14.07.2009; National Acad Sciences
• Subjects: Adoptive Transfer; Animals; Antibodies; Antigen presenting cells; Autoimmune diseases; Biological Sciences; Catalytic activity; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cell Proliferation - drug effects; Cells; Colitis; Colitis - immunology; Colitis - prevention & control; Complementary DNA; Disease models; DNA Primers - genetics; Flow Cytometry; Group II Phospholipases A2 - metabolism; Group II Phospholipases A2 - pharmacology; Inflammatory bowel disease; Mice; Molecules; Multiple sclerosis; Multiple Sclerosis - immunology; Multiple Sclerosis - prevention & control; Proteins; Receptors; Recombinant Fusion Proteins - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Signal transduction; Signal Transduction - immunology; T lymphocytes; T-Lymphocytes, Regulatory - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0812569106

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.