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Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for suppression
Open accessAbstract
CD4+ effector T cells (Teff cells) and regulatory T cells (Treg 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 Teff cell proliferation and inflammatory function, the mechanisms that regulate Treg cell metabolism and function remain unclear. We found that Toll-like receptor (TLR) signals that promote Treg cell proliferation increased PI(3)K-Akt-mTORC1 signaling, glycolysis and expression of Glut1. However, TLR-induced mTORC1 signaling also impaired Treg 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 Treg 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 Treg cells.
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Metadata
- Authors
- Gerriets, V. A., Kishton, R. J., Johnson, M. O., Cohen, S., Siska, P. J., Nichols, A. G., Warmoes, M. O., de Cubas, A. A., MacIver, N. J., Locasale, J. W., Turka, L. A., Wells, A. D., & Rathmell, J. C.
- Venue
- Nature Immunology
- Published
- 2016-10-03
- Volume
- 17
- Issue
- 12
- Pages
- 1459-1466
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2529711900
- Cited by
- 539
- References
- 10
- FWCI
- 22.71
- Type
- journal article
- Language
- en
- Open access
- green
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