Secretory phospholipase A2-IID is an effector molecule of CD4+CD25+ regulatory T cells.
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.
von Allmen
Caroline E
CE
Cytos Biotechnology AG, Wagistrasse 25, CH-8952 Schlieren, Switzerland.
Schmitz
Nicole
N
Bauer
Monika
M
Hinton
Heather J
HJ
Kurrer
Michael O
MO
Buser
Regula B
RB
Gwerder
Myriam
M
Muntwiler
Simone
S
Sparwasser
Tim
T
Beerli
Roger R
RR
Bachmann
Martin F
MF
D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects*; D003092:Colitis / Q000276:immunology / Q000517:prevention & control*; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D054501:Group II Phospholipases A2 / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
D017931:DNA Primers; D011993:Recombinant Fusion Proteins; D054501:Group II Phospholipases A2