Cutting Edge: TGF-β and Phosphatidylinositol 3-Kinase Signals Modulate Distinct Metabolism of Regulatory T Cell Subsets

Bhavana Priyadharshini, Michael Loschi, Ryan H. Newton, Jian Wen Zhang, Kelsey K. Finn, Valerie A Gerriets, Alexandria Huynh, Jeffrey C. Rathmell, Bruce R Blazar, Laurence A. Turka

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Murine Foxp3+ regulatory T cells (Tregs) differentiated in vitro (induced Tregs [iTregs]) in the presence of antiinflammatory cytokine TGF-β rely predominantly upon lipid oxidation to fuel mitochondrial oxidative phosphorylation. Foxp3 expression underlies this metabolic preference, as it suppresses glycolysis and drives oxidative phosphorylation. In this study, we show that in contrast to iTregs, thymic-derived Tregs (tTregs), engage in glycolysis and glutaminolysis at levels comparable to effector T cells despite maintained Foxp3 expression. Interestingly, exposure of tTregs to the anti-inflammatory cytokine TGF-β represses PI3K-mediated mTOR signaling, inhibits glucose transporter and Hk2 expression, and reprograms their metabolism to favor oxidative phosphorylation. Conversely, replicating the effects of inflammation via elevation of PI3K signaling has minimal effects on tTregs but dramatically enhances the glycolysis of normally oxidative iTregs, resulting in reduction of Foxp3 expression. Collectively, these findings suggest both extrinsic and intrinsic factors govern the unique metabolic signature of Treg subsets.

Original languageEnglish (US)
Pages (from-to)2215-2219
Number of pages5
JournalJournal of Immunology
Volume201
Issue number8
DOIs
StatePublished - Oct 15 2018

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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    Priyadharshini, B., Loschi, M., Newton, R. H., Zhang, J. W., Finn, K. K., Gerriets, V. A., Huynh, A., Rathmell, J. C., Blazar, B. R., & Turka, L. A. (2018). Cutting Edge: TGF-β and Phosphatidylinositol 3-Kinase Signals Modulate Distinct Metabolism of Regulatory T Cell Subsets. Journal of Immunology, 201(8), 2215-2219. https://doi.org/10.4049/jimmunol.1800311