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Spatiotemporal regulation of energetic charge dictates T cell function
Aleksandra S Chikina1, Béatrice Corre1, Fabrice Lemaître1
1Institut Pasteur, Université de Paris Cité, INSERM U1223, Paris, France.
Nature Communications
|January 21, 2026
Summary
Immune cell energy levels vary by location and time of day, impacting T cell function. Understanding these energetic differences is key to modulating immune responses.
Area of Science:
- Immunology
- Cellular Metabolism
- Systems Biology
Background:
- Immune cell function is linked to differentiation, transcriptional, and epigenetic regulation.
- Cellular metabolism is crucial for immune cell energy production, but energy charge dynamics remain unclear.
Purpose of the Study:
- To investigate variations in immune cell energy charge across different anatomical locations and times.
- To determine if immune cell energy charge influences cellular function.
Main Methods:
- Utilized SPICE-Met to analyze ATP: ADP ratio, a cellular energy indicator, in complex cell populations in vivo.
- Compared energetic charge of T cells in blood versus lymph nodes and across different times of day.
Main Results:
- Immune cells with high glycolytic capacity (effector T cells, NK cells) showed the highest ATP: ADP ratios.
- Effector T cells exhibited higher energetic charge in blood than lymph nodes, linked to glucose availability.
- Circadian rhythms influenced energy charge, peaking during the early rest phase.
- Variations in energetic charge directly impacted T cell function, specifically IFN-γ production.
Conclusions:
- Immune cell energetic resources and function differ across anatomical sites and circadian times.
- Nutrient availability and energy charge are critical regulators of immune cell function in vivo.
- Modulating energy charge and nutrient availability offers a potential strategy to control immune responses.
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