Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for suppression
T cells undergo metabolic reprogramming after they are activated. Rathmell and colleagues show that inflammatory Toll-like receptor signals induce glycolysis and impair the suppression of regulatory T cells, but Foxp3 can promote a switch to oxidative phosphorylation and suppression. CD4 + effector...
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Published in | Nature immunology Vol. 17; no. 12; pp. 1459 - 1466 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Nature Publishing Group US
03.10.2016
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | T cells undergo metabolic reprogramming after they are activated. Rathmell and colleagues show that inflammatory Toll-like receptor signals induce glycolysis and impair the suppression of regulatory T cells, but Foxp3 can promote a switch to oxidative phosphorylation and suppression.
CD4
+
effector T cells (T
eff
cells) and regulatory T cells (T
reg
cells) undergo metabolic reprogramming to support proliferation and immunological function. Although signaling via the lipid kinase PI(3)K (phosphatidylinositol-3-OH kinase), the serine-threonine kinase Akt and the metabolic checkpoint kinase complex mTORC1 induces both expression of the glucose transporter Glut1 and aerobic glycolysis for T
eff
cell proliferation and inflammatory function, the mechanisms that regulate T
reg
cell metabolism and function remain unclear. We found that Toll-like receptor (TLR) signals that promote T
reg
cell proliferation increased PI(3)K-Akt-mTORC1 signaling, glycolysis and expression of Glut1. However, TLR-induced mTORC1 signaling also impaired T
reg
cell suppressive capacity. Conversely, the transcription factor Foxp3 opposed PI(3)K-Akt-mTORC1 signaling to diminish glycolysis and anabolic metabolism while increasing oxidative and catabolic metabolism. Notably, Glut1 expression was sufficient to increase the number of T
reg
cells, but it reduced their suppressive capacity and Foxp3 expression. Thus, inflammatory signals and Foxp3 balance mTORC1 signaling and glucose metabolism to control the proliferation and suppressive function of T
reg
cells. |
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Bibliography: | These authors contributed equally to this work. |
ISSN: | 1529-2908 1529-2916 |
DOI: | 10.1038/ni.3577 |