Article | Published:

Bcl-6 directly represses the gene program of the glycolysis pathway

Nature Immunology volume 15, pages 957964 (2014) | Download Citation

Abstract

Despite the increasing knowledge of the molecular events that induce the glycolysis pathway in effector T cells, very little is known about the transcriptional mechanisms that dampen the glycolysis program in quiescent cell populations such as memory T cells. Here we found that the transcription factor Bcl-6 directly repressed genes encoding molecules involved in the glycolysis pathway, including Slc2a1, Slc2a3, Pkm and Hk2, in type 1 helper T cells (TH1 cells) exposed to low concentrations of interleukin 2 (IL-2). Thus, Bcl-6 had a role opposing the IL-2-sensitive glycolytic transcriptional program that the transcription factors c-Myc and HIF-1α promote in effector T cells. Additionally, the TH1 lineage–specifying factor T-bet functionally antagonized the Bcl-6-dependent repression of genes encoding molecules in the glycolysis pathway, which links the molecular balance of these two factors to regulation of the metabolic gene program.

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Acknowledgements

We thank D. Rawlings (University of Washington) for human Ramos B cells; the preclinical repository of the National Cancer Institute for IL-2 and anti-IL-4; M. Wijaranakula for technical assistance; D. Chisolm for critical reading of the manuscript; and A. Ballesteros-Tato, B. Leon and T. Dadali-Abel for advice and assistance. Supported by the National Institute of Allergy and Infectious Diseases (AI061061 to A.S.W.) and the American Cancer Society (RSG-09-045-01-DDC to A.S.W.).

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Affiliations

  1. Department of Immunology, University of Washington, Seattle, Washington, USA.

    • Kenneth J Oestreich
    • , Sarah E Gilbertson
    •  & Amy S Weinmann
  2. Virginia Tech Carilion Research Institute, Roanoke, Virginia, USA.

    • Kenneth J Oestreich
    • , Kaitlin A Read
    •  & Paul W McDonald
  3. Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA.

    • Kenneth J Oestreich
  4. Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

    • Kenneth P Hough
    • , Veena Krishnamoorthy
    •  & Amy S Weinmann

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Contributions

K.J.O. and A.S.W. conceived of and designed the study, performed experiments, analyzed data and wrote the manuscript; and K.A.R., S.E.G., K.P.H., P.W.M. and V.K. performed experiments and analyzed data sets.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Kenneth J Oestreich or Amy S Weinmann.

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https://doi.org/10.1038/ni.2985

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