ArticleImmunity2022
MTHFD2 is a metabolic checkpoint controlling effector and regulatory T cell fate and function.
Article in Immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.
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Who cites it
121 citing papers in PubMed, 203 citations in OpenAlex.
- Cryoablation and post-progression immune checkpoint inhibition in metastatic melanoma: a phase II trial.Nature communications · 2024Trial
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Dynamic control of nucleotide metabolism in physiology and disease.Nature cell biology · 2026Review
- A five-gene TAM and MYCN signature predicts prognosis and identifies MTHFD2 as a therapeutic target in neuroblastoma.Discover oncology · 2026Article
- Spatial architecture of immunometabolism: Mitochondrial‑organelle interfaces in immune signaling (Review).International journal of molecular medicine · 2026Review
- Targeting NFATc1-regulated MTHFD2 one-carbon metabolism to suppress sustained T-cell-mediated inflammation in rheumatoid arthritis.Signal transduction and targeted therapy · 2026Article
- Leveraging Lineage Barcodes as Natural Augmentations for Contrastive Learning of Cell Fate in scRNA-seq Data.bioRxiv : the preprint server for biology · 2026Article
- Review
- Synthetic lethality in cancer: mechanism exploration and therapeutic applications.Cell communication and signaling : CCS · 2026Review
- CPT1A loss promotes lung metastasis in immune-competent mice via a mechanism of mtDNA release and chronic activation of STING pathway.bioRxiv : the preprint server for biology · 2026Article
- ssNetShift: single-sample metabolic network rewiring reveals hidden prognostic subtypes beyond clinical staging in gastric cancer.Briefings in bioinformatics · 2026Article
- Review
- MTHFD2: a promising metabolic checkpoint for diseases.Journal of translational medicine · 2026Review
- Metabolic reprogramming of Th17/Treg imbalance in autoimmune thyroid diseases.Cell communication and signaling : CCS · 2026Review
- Tissue and CD4 T cell subset dependence on the amino acid transporter SLC38A1.Cell metabolism · 2026Article
- Th17/Treg cell imbalance in allergic rhinitis: mechanisms and therapeutic implications.Genes and immunity · 2026Review
- Integrative analysis of transcriptome and single-cell sequencing combined with experimental validation identifies biomarkers associated with T cell and senescence in sepsis.Scientific reports · 2026Article
- Alternative Pathway for Methyl Supply through the Coupling of SHMT1 and PEMT to Maintain Astrocytic Homeostasis in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Article
61 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 3 institutions in 1 country.
Funding
Abstract
Antigenic stimulation promotes T cell metabolic reprogramming to meet increased biosynthetic, bioenergetic, and signaling demands. We show that the one-carbon (1C) metabolism enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) regulates de novo purine synthesis and signaling in activated T cells to promote proliferation and inflammatory cytokine production. In pathogenic T helper-17 (Th17) cells, MTHFD2 prevented aberrant upregulation of the transcription factor FoxP3 along with inappropriate gain of suppressive capacity. MTHFD2 deficiency also promoted regulatory T (Treg) cell differentiation. Mechanistically, MTHFD2 inhibition led to depletion of purine pools, accumulation of purine biosynthetic intermediates, and decreased nutrient sensor mTORC1 signaling. MTHFD2 was also critical to regulate DNA and histone methylation in Th17 cells. Importantly, MTHFD2 deficiency reduced disease severity in multiple in vivo inflammatory disease models. MTHFD2 is thus a metabolic checkpoint to integrate purine metabolism with pathogenic effector cell signaling and is a potential therapeutic target within 1C metabolism pathways.
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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.