학술논문

Secretory phospholipase A2-IID is an effector molecule of [CD4.sup.+][CD25.sup.+] regulatory T cells
Document Type
Author abstract
Report
Source
Proceedings of the National Academy of Sciences of the United States. July 14, 2009, Vol. 106 Issue 28, p11673, 6 p.
Subject
Immunosuppression -- Health aspects
Immunosuppression -- Research
Multiple sclerosis -- Care and treatment
Multiple sclerosis -- Research
Phospholipases -- Physiological aspects
Phospholipases -- Research
T cells -- Physiological aspects
T cells -- Research
Science and technology
Language
English
ISSN
0027-8424
Abstract
Suppression by natural [CD4.sup.+][CD25.sup.+] 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.sup.+] and [CD8.sup.+] 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. differential screening | suppression | tolerance