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Nur77 serves as a molecular brake of the metabolic switch during T cell activation to restrict autoimmunity

Marie Liebmann1, Stephanie Hucke1, Kathrin Koch1

  • 1Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, 48149 Muenster, Germany.

Proceedings of the National Academy of Sciences of the United States of America
|August 4, 2018
PubMed

Insights

The transcription factor Nur77 regulates T cell metabolism, controlling their activation and energy use. Nur77 deficiency enhances T cell activation, increasing susceptibility to inflammatory diseases.

Area of Science:

  • Immunology
  • Cellular Metabolism
  • Molecular Biology

Background:

  • T cell activation and expansion require significant metabolic reprogramming.
  • Cell-intrinsic factors play a crucial role in modulating T cell responses.

Purpose of the Study:

  • To identify novel regulators of T cell activation and metabolism.
  • To investigate the role of the transcription factor Nur77 in T cell function and inflammatory diseases.

Main Methods:

  • Investigated T cell activation and proliferation in Nur77-deficient models.
  • Analyzed T cell energy metabolism, including mitochondrial respiration and glycolysis.
  • Performed transcriptional network analysis to identify target genes of Nur77.

Main Results:

  • Nur77 acts as a cell-intrinsic modulator of T cell activation.
  • Nur77-deficient T cells exhibit enhanced proliferation and activation.
  • Lack of Nur77 increases susceptibility to T cell-mediated inflammatory diseases like CNS autoimmunity and arthritis.
  • Nur77 regulates T cell energy metabolism by controlling mitochondrial respiration and glycolysis.
  • Nur77 modulates metabolic gene expression, potentially interacting with factors like estrogen-related receptor α.

Conclusions:

  • Nur77 is a key transcriptional regulator of T cell metabolism.
  • Nur77 elevates the threshold for T cell activation.
  • Nur77 confers protection against T cell-mediated inflammatory diseases.
Keywords:
Nur77T cellsautoimmunityimmunometabolism

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