ArticleThe Journal of experimental medicine2013
Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 211 papers, 1 of them a synthesis that pooled it.
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Who cites it
211 citing papers in PubMed, 1 synthesis or guideline pooled it, 327 citations in OpenAlex.
- Type 2 Diabetes: How Much of an Autoimmune Disease?Frontiers in endocrinology · 2019Pooled it
- Rheumatoid arthritis T cell and muscle oxidative metabolism associate with exercise-induced changes in cardiorespiratory fitness.Scientific reports · 2022Trial
- Temperature extremes and autoimmune diseases.Seminars in immunopathology · 2026Review
- Metabolic switch: lymphocytes and the onset of T-cell-mediated autoimmunity.Cellular & molecular immunology · 2026Review
- Persistent CD4Cellular immunology · 2026Article
- Immune responses in aging adults.The Journal of clinical investigation · 2026Review
- Causal inference of metabolites in autoimmune liver diseases: A Mendelian randomization analysis.Medicine · 2026Article
- Lipid droplet-induced T cell death sustains autoimmune tissue inflammation.Cell metabolism · 2026Article
- RNA-Based Biomarkers for Diagnostic Discrimination of Ischemic and Hemorrhagic Stroke: A Systematic Review.Journal of clinical medicine · 2026Review
- High glucose-induced mitophagy accelerates premature aging of T cells in patients with rheumatoid arthritis.Clinical rheumatology · 2026Article
- Glucose Metabolic Enzyme PFKFB3 in Cardiopulmonary Vascular Health and Disease.Circulation research · 2026Review
- Succinate-mediated metabolic alterations and signaling in RA: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- The role of energy deficit in autophagy failure in Parkinson's disease.Frontiers in aging neuroscience · 2026Review
- Article
- Preservation of Autophagy May Be a Mechanism Behind Healthy Aging.Aging cell · 2025Article
- Blood immunomap for prediction of responses to anti-PD-1 immunotherapy in metastatic non-small cell lung cancer.iScience · 2025Article
- Mitochondria as a Disease-Relevant Organelle in Rheumatoid Arthritis: A Key Breakout in Fight Against the Disease.Biomedicines · 2025Review
- Immune Aging in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Review
- SIRT3 deficiency reduces PFKFB3-driven T-cell glycolysis and promotes arthritic inflammation.Science China. Life sciences · 2025Article
- 1,400 genetically predicted plasma metabolites in relation to risk of primary biliary cholangitis: a bi-directional, two-sample Mendelian randomization analysis.Clinical and experimental hepatology · 2025Article
151 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
In the HLA class II-associated autoimmune syndrome rheumatoid arthritis (RA), CD4 T cells are critical drivers of pathogenic immunity. We have explored the metabolic activity of RA T cells and its impact on cellular function and fate. Naive CD4 T cells from RA patients failed to metabolize equal amounts of glucose as age-matched control cells, generated less intracellular ATP, and were apoptosis-susceptible. The defect was attributed to insufficient induction of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a regulatory and rate-limiting glycolytic enzyme known to cause the Warburg effect. Forced overexpression of PFKFB3 in RA T cells restored glycolytic flux and protected cells from excessive apoptosis. Hypoglycolytic RA T cells diverted glucose toward the pentose phosphate pathway, generated more NADPH, and consumed intracellular reactive oxygen species (ROS). PFKFB3 deficiency also constrained the ability of RA T cells to resort to autophagy as an alternative means to provide energy and biosynthetic precursor molecules. PFKFB3 silencing and overexpression identified a novel extraglycolytic role of the enzyme in autophagy regulation. In essence, T cells in RA patients, even those in a naive state, are metabolically reprogrammed with insufficient up-regulation of the glycolytic activator PFKFB3, rendering them energy-deprived, ROS- and autophagy-deficient, apoptosis-sensitive, and prone to undergo senescence.
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Registered trials
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.