ArticleCell reports2021
Regulatory T cell differentiation is controlled by αKG-induced alterations in mitochondrial metabolism and lipid homeostasis.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 106 citations in OpenAlex.
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- Spatial architecture of immunometabolism: Mitochondrial‑organelle interfaces in immune signaling (Review).International journal of molecular medicine · 2026Review
- From metabolic node to smart building block: α-Ketoglutarate-empowered biomaterials for programmable cell fate.Materials today. Bio · 2026Review
- Endogenous metabolite signaling orchestrates tumor immune evasion.Cell insight · 2026Review
- Targeting colorectal cancer and T‑cell metabolism for the treatment of colorectal cancer (Review).Oncology reports · 2026Review
- Acute capillary blood DNA methylation responses to swimming exercise in high-performance male and female swimmers.Experimental physiology · 2026Article
- CHAC2-mediated glutathione metabolic reprogramming drives N1 polarization of bone marrow neutrophils and exacerbates inflammatory comorbidities.International journal of oral science · 2026Article
- DNMT3A/TET2-mediated epigenetic alteration in Type-1 diabetes dysregulates the haematopoiesis.Molecular biology reports · 2026Review
- The mechano-immunological landscape in the tumor microenvironment: From mechanical sensing to a new therapeutic paradigm.Materials today. Bio · 2026Review
- Metabolic modulation of immune cell function: mechanisms and therapeutic implications in cancer immunotherapy.Oncogenesis · 2026Review
- Metabolic reprogramming of Th17/Treg imbalance in autoimmune thyroid diseases.Cell communication and signaling : CCS · 2026Review
- Combining Small-Molecular Compounds With CAR T-Cell Therapy: Novel Strategies for Enhanced Cancer Immunotherapy.Cancer innovation · 2026Review
- Metabolic reprogramming of CAR-T cells: a multi-pronged strategy to conquer the immunosuppressive tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- The impact of p53 mutation on tumor immune evasion: mechanistic insights and clinical implications.Frontiers in immunology · 2026Review
- Tumor-immune metabolic tug-of-war: from immune escape to targeting metabolic rewiring in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Alpha-ketoglutarate Potentiates IL-1β Production and Suppressive Mechanisms of Myeloid-Derived Suppressor Cells by Altering Redox Metabolism and Inducing Autophagy.International journal of biological sciences · 2026Article
- Integrating multi-omics, machine learning, and molecular dynamics simulations to identify glutamate metabolism-related biomarkers and drug candidates in rheumatoid arthritis.Frontiers in molecular biosciences · 2026Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
27 authors at 8 institutions in 6 countries.
Funding
Abstract
Suppressive regulatory T cell (Treg) differentiation is controlled by diverse immunometabolic signaling pathways and intracellular metabolites. Here we show that cell-permeable α-ketoglutarate (αKG) alters the DNA methylation profile of naive CD4 T cells activated under Treg polarizing conditions, markedly attenuating FoxP3+ Treg differentiation and increasing inflammatory cytokines. Adoptive transfer of these T cells into tumor-bearing mice results in enhanced tumor infiltration, decreased FoxP3 expression, and delayed tumor growth. Mechanistically, αKG leads to an energetic state that is reprogrammed toward a mitochondrial metabolism, with increased oxidative phosphorylation and expression of mitochondrial complex enzymes. Furthermore, carbons from ectopic αKG are directly utilized in the generation of fatty acids, associated with lipidome remodeling and increased triacylglyceride stores. Notably, inhibition of either mitochondrial complex II or DGAT2-mediated triacylglyceride synthesis restores Treg differentiation and decreases the αKG-induced inflammatory phenotype. Thus, we identify a crosstalk between αKG, mitochondrial metabolism and triacylglyceride synthesis that controls Treg fate.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.