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Foxp3 Reprograms T Cell Metabolism to Function in Low-Glucose, High-Lactate Environments
Alessia Angelin1, Luis Gil-de-Gómez2, Satinder Dahiya3
1Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Cell Metabolism
|April 19, 2017
Summary
T-regulatory cells (Tregs) adapt to low-glucose, high-lactate environments by altering metabolism, enhancing their function in maintaining immune tolerance. This metabolic reprogramming by Foxp3 helps Tregs resist suppression and may inform cancer and autoimmune disease treatments.
Area of Science:
- Immunology
- Cell Metabolism
- Molecular Biology
Background:
- Immune cells operate in varied metabolic conditions, including low-glucose, high-lactate environments found in tissues like the gut or during ischemia.
- T-regulatory cells (Tregs) are crucial for peripheral tolerance, but their metabolic adaptations in such environments are not well understood.
Purpose of the Study:
- To investigate how T-regulatory cells (Tregs) function and adapt metabolically in low-glucose, lactate-rich conditions.
- To elucidate the role of the transcription factor Foxp3 in Treg metabolic reprogramming.
Main Methods:
- Analysis of Treg transcription factor Foxp3's role in metabolic pathway regulation.
- Assessment of metabolic shifts including glycolysis, oxidative phosphorylation, and NAD+ oxidation in Tregs.
- Evaluation of Treg function and proliferation in simulated low-glucose, lactate-rich microenvironments.
Main Results:
- Foxp3 reprograms Treg metabolism by suppressing Myc and glycolysis while enhancing oxidative phosphorylation and NAD+ oxidation.
- These metabolic adaptations confer a functional advantage to Tregs in low-glucose, lactate-rich settings.
- Tregs with this metabolic phenotype resist lactate-mediated suppression of function and proliferation.
Conclusions:
- Treg metabolic reprogramming via Foxp3 is critical for immune tolerance in challenging microenvironments.
- This metabolic adaptation may explain Treg roles in tissue injury and immune evasion by cancer cells.
- Understanding Treg metabolism offers potential for novel immunomodulatory strategies in cancer and autoimmune diseases.