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Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for suppression.

Publication ,  Journal Article
Gerriets, VA; Kishton, RJ; Johnson, MO; Cohen, S; Siska, PJ; Nichols, AG; Warmoes, MO; de Cubas, AA; MacIver, NJ; Locasale, JW; Turka, LA ...
Published in: Nat Immunol
December 2016

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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Published In

Nat Immunol

DOI

EISSN

1529-2916

Publication Date

December 2016

Volume

17

Issue

12

Start / End Page

1459 / 1466

Location

United States

Related Subject Headings

  • Toll-Like Receptors
  • TOR Serine-Threonine Kinases
  • T-Lymphocytes, Regulatory
  • T-Lymphocytes, Helper-Inducer
  • Signal Transduction
  • Proto-Oncogene Proteins c-akt
  • Multiprotein Complexes
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gerriets, V. A., Kishton, R. J., Johnson, M. O., Cohen, S., Siska, P. J., Nichols, A. G., … Rathmell, J. C. (2016). Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for suppression. Nat Immunol, 17(12), 1459–1466. https://doi.org/10.1038/ni.3577
Gerriets, Valerie A., Rigel J. Kishton, Marc O. Johnson, Sivan Cohen, Peter J. Siska, Amanda G. Nichols, Marc O. Warmoes, et al. “Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for suppression.Nat Immunol 17, no. 12 (December 2016): 1459–66. https://doi.org/10.1038/ni.3577.
Gerriets VA, Kishton RJ, Johnson MO, Cohen S, Siska PJ, Nichols AG, et al. Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for suppression. Nat Immunol. 2016 Dec;17(12):1459–66.
Gerriets, Valerie A., et al. “Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for suppression.Nat Immunol, vol. 17, no. 12, Dec. 2016, pp. 1459–66. Pubmed, doi:10.1038/ni.3577.
Gerriets VA, Kishton RJ, Johnson MO, Cohen S, Siska PJ, Nichols AG, Warmoes MO, de Cubas AA, MacIver NJ, Locasale JW, Turka LA, Wells AD, Rathmell JC. Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for suppression. Nat Immunol. 2016 Dec;17(12):1459–1466.

Published In

Nat Immunol

DOI

EISSN

1529-2916

Publication Date

December 2016

Volume

17

Issue

12

Start / End Page

1459 / 1466

Location

United States

Related Subject Headings

  • Toll-Like Receptors
  • TOR Serine-Threonine Kinases
  • T-Lymphocytes, Regulatory
  • T-Lymphocytes, Helper-Inducer
  • Signal Transduction
  • Proto-Oncogene Proteins c-akt
  • Multiprotein Complexes
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice