ArticlePloS one2017
Reactive oxygen species are required for driving efficient and sustained aerobic glycolysis during CD4+ T cell activation.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 88 citations in OpenAlex.
- Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations.The Journal of clinical investigation · 2020Trial
- Molecular mechanisms and targeted therapeutic strategies for glycolytic reprogramming in osteosarcoma.Genes & diseases · 2027Review
- Metabolic switch: lymphocytes and the onset of T-cell-mediated autoimmunity.Cellular & molecular immunology · 2026Review
- Boosting T cell antioxidant capacity: A strategic approach to overcome immunosuppression in solid tumors.Redox biology · 2026Review
- The spatiotemporal heterogeneity of reactive oxygen species in the malignant transformation of viral hepatitis to hepatocellular carcinoma: a new insight.Cellular & molecular biology letters · 2025Review
- Targeting CD4+ T Cell Glucose Metabolism: A Novel Immunotherapeutic Approach for Type 1 Diabetes.Biomolecules · 2025Review
- From powerhouse to modulator: regulating immune system responses through intracellular mitochondrial transfer.Cell communication and signaling : CCS · 2025Review
- Dysfunctional β-cell autophagy induces β-cell stress and enhances islet immunogenicity.Frontiers in immunology · 2025Article
- Metabolic reprogramming of CAR T cells: a new frontier in cancer immunotherapy.Frontiers in immunology · 2025Review
- Antibody-targeted T cells and natural killer cells for cancer immunotherapy.Journal of nanobiotechnology · 2024Article
- Mechanisms of oxidative stress in interstitial cystitis/bladder pain syndrome.Nature reviews. Urology · 2024Review
- Metabolic engineering for optimized CAR-T cell therapy.Nature metabolism · 2024Review
- Extracellular Delivery of Functional Mitochondria Rescues the Dysfunction of CD4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The relationship of redox signaling with the risk for atherosclerosis.Frontiers in pharmacology · 2024Review
- The role of mitochondria in eosinophil function: implications for severe asthma pathogenesis.Frontiers in cell and developmental biology · 2024Review
- Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes.Frontiers in molecular biosciences · 2024Review
- Recovery of intracellular glucose uptake in T cells during partial remission of type 1 diabetes.Diabetologia · 2023Article
- Review
- Glucose metabolic reprogramming in autoimmune diseases.Animal cells and systems · 2023Review
- Role of CAR T Cell Metabolism for Therapeutic Efficacy.Cancers · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The immune system is necessary for protecting against various pathogens. However, under certain circumstances, self-reactive immune cells can drive autoimmunity, like that exhibited in type 1 diabetes (T1D). CD4+ T cells are major contributors to the immunopathology in T1D, and in order to drive optimal T cell activation, third signal reactive oxygen species (ROS) must be present. However, the role ROS play in mediating this process remains to be further understood. Recently, cellular metabolic programs have been shown to dictate the function and fate of immune cells, including CD4+ T cells. During activation, CD4+ T cells must transition metabolically from oxidative phosphorylation to aerobic glycolysis to support proliferation and effector function. As ROS are capable of modulating cellular metabolism in other models, we sought to understand if blocking ROS also regulates CD4+ T cell activation and effector function by modulating T cell metabolism. To do so, we utilized an ROS scavenging and potent antioxidant manganese metalloporphyrin (MnP). Our results demonstrate that redox modulation during activation regulates the mTOR/AMPK axis by maintaining AMPK activation, resulting in diminished mTOR activation and reduced transition to aerobic glycolysis in diabetogenic splenocytes. These results correlated with decreased Myc and Glut1 upregulation, reduced glucose uptake, and diminished lactate production. In an adoptive transfer model of T1D, animals treated with MnP demonstrated delayed diabetes progression, concurrent with reduced CD4+ T cell activation. Our results demonstrate that ROS are required for driving and sustaining T cell activation-induced metabolic reprogramming, and further support ROS as a target to minimize aberrant immune responses in autoimmunity.
Indexed as
Identifiers
What OpenQuestion holds
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.