iScience (Mar 2022)

Nicotinamide breaks effector CD8 T cell responses by targeting mTOR signaling

  • Federica Agliano,
  • Timofey A. Karginov,
  • Antoine Ménoret,
  • Anthony Provatas,
  • Anthony T. Vella

Journal volume & issue
Vol. 25, no. 3
p. 103932

Abstract

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Summary: Nicotinamide (NAM) shapes T cell responses but its precise molecular mechanism of action remains elusive. Here, we show that NAM impairs naive T cell effector transition but also effector T cells themselves. Although aerobic glycolysis is a hallmark of activated T cells, CD8+ T cells exposed to NAM displayed enhanced glycolysis, yet producing significantly less IFNγ. Mechanistically, NAM reduced mTORC1 activity independently of NAD+ metabolism, decreasing IFNγ translation and regulating T cell transcriptional factors critical to effector/memory fate. Finally, the role of NAM in a biomedically relevant model of lung injury was tested. Specifically, a NAM-supplemented diet reduced systemic IL-2, antigen-specific T cell clonal expansion, and effector function after inhalation of Staphylococcus aureus enterotoxin A. These findings identify NAM as a potential therapeutic supplement that uncouples glycolysis from effector cytokine production and may be a powerful treatment for diseases associated with T cell hyperactivation.

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