Related Experiment Video
Updated: Oct 1, 2025
06:07
Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells
Published on: March 28, 2025
509
Nicotinamide breaks effector CD8 T cell responses by targeting mTOR signaling
Federica Agliano1, Timofey A Karginov1, Antoine Ménoret1
1Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT 06030 USA.
Iscience
|March 4, 2022
Summary
Nicotinamide (NAM) impairs T cell effector function by reducing mTORC1 activity and IFNγ production, even with increased glycolysis. This suggests NAM as a potential therapy for T cell hyperactivation diseases.
Area of Science:
- Immunology
- Cellular Metabolism
- Molecular Biology
Background:
- Nicotinamide (NAM) influences T cell responses, but its exact molecular mechanisms are unclear.
- T cell activation typically involves aerobic glycolysis, a metabolic process crucial for energy production.
Purpose of the Study:
- To elucidate the molecular mechanisms by which NAM affects T cell function.
- To investigate the impact of NAM on T cell metabolism and effector functions, including cytokine production.
- To evaluate the therapeutic potential of NAM in a model of lung injury.
Main Methods:
- Investigated the effects of NAM on naive and effector CD8+ T cells.
- Assessed glycolysis, IFNγ production, mTORC1 activity, and T cell transcriptional factors.
- Utilized a mouse model of lung injury induced by *Staphylococcus aureus* enterotoxin A (SEA).
Main Results:
- NAM impaired T cell effector transition and function, reducing IFNγ production despite enhanced glycolysis.
- NAM decreased mTORC1 activity independently of NAD+ metabolism, affecting IFNγ translation and T cell fate.
- In a lung injury model, a NAM-supplemented diet reduced IL-2, T cell expansion, and effector function post-SEA exposure.
Conclusions:
- Nicotinamide uncouples glycolysis from effector cytokine production in T cells.
- NAM modulates T cell transcriptional factors crucial for effector and memory cell differentiation.
- NAM shows potential as a therapeutic supplement for diseases characterized by T cell hyperactivation.
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