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Updated: Mar 10, 2026
Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells
Published on: April 16, 2012
Ammonia: a metabolic checkpoint for Treg potency.
Ali Valipour Motlagh1, Eyad Elkord2, Weiwei Dai3
1Department of Biosciences and Bioinformatics, School of Science, Xi'an Jiaotong-Liverpool University, Ren'ai Road, Suzhou, Jiangsu 215123, People's Republic of China; Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology (ISMIB), University of Liverpool, Liverpool, UK.
Ammonia fuels regulatory T cells (Tregs), enabling them to convert waste into immune suppression. This process drives tumor immune evasion and resistance to immunotherapy.
Area of Science:
- Immunology
- Metabolic pathways
- Cancer research
Background:
- Regulatory T cells (Tregs) are crucial for immune homeostasis and preventing autoimmunity.
- Tregs play a significant role in tumor immune evasion and immunotherapy resistance.
- Metabolic reprogramming is increasingly recognized as a key factor in Treg function.
Purpose of the Study:
- To elucidate the metabolic mechanisms by which Tregs suppress anti-tumor immunity.
- To identify novel therapeutic targets for overcoming immunotherapy resistance in cancer.
Main Methods:
- Investigated the role of ammonia metabolism in Treg function.
- Utilized argininosuccinate lyase (ASL)-linked survival buffering.
- Examined the FOXP3-spermine-PPARγ axis for mitochondrial reinforcement in Tregs.
Main Results:
- Ammonia serves as a critical metabolic checkpoint for Treg activation and function.
- Tregs employ ASL-linked survival buffering to manage metabolic stress.
- The FOXP3-spermine-PPARγ axis reinforces Treg mitochondria, converting waste into suppressive capacity.
- This metabolic reprogramming enhances tumor immune evasion and immunotherapy resistance.
Conclusions:
- Treg metabolic reprogramming, particularly ammonia utilization, is essential for tumor immune evasion.
- Targeting Treg metabolic pathways, such as the identified axis, may overcome immunotherapy resistance.
