ArticleArthritis research & therapy2021
Increase of aerobic glycolysis mediated by activated T helper cells drives synovial fibroblasts towards an inflammatory phenotype: new targets for therapy?
Article in Arthritis research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
- Inhibition of Hexokinase 2 Undermines Cartilage Health and Accelerates Osteoarthritis.Cartilage · 2026Article
- The role of lactate on arthritis-associated cells: physiology, pathology, and therapeutic strategies.Cellular and molecular life sciences : CMLS · 2026Review
- Lactylation modification - a bridge between sepsis and macrophage metabolic reprogramming.Frontiers in immunology · 2026Review
- Transcriptional and epigenetic control of human naïve CD8Frontiers in immunology · 2026Article
- Liver-joint axis: Hepatitis B virus as a contributor to rheumatoid arthritis pathogenesis.Virulence · 2025Review
- Lactylation at the crossroads of immune metabolism and epigenetic regulation: revealing its role in rheumatic immune diseases.Journal of translational medicine · 2025Review
- Histone lactylation promotes rheumatoid arthritis progression by increasing NFATc2 expression and the production of anti-lactylated histone autoantibodies.Nature communications · 2025Article
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Habbe Gule Aakh prevents glycolytic program and alleviates disease progression in a rheumatoid arthritis animal model.Frontiers in immunology · 2025Article
- Metabolic regulation of the immune system in health and diseases: mechanisms and interventions.Signal transduction and targeted therapy · 2024Review
- Targeting Lactate: An Emerging Strategy for Macrophage Regulation in Chronic Inflammation and Cancer.Biomolecules · 2024Review
- Treatment of Rheumatoid Arthritis Based on the Inherent Bioactivity of Black Phosphorus Nanosheets.Aging and disease · 2024Article
- Metabolic changes in fibroblast-like synoviocytes in rheumatoid arthritis: state of the art review.Frontiers in immunology · 2024Review
- Lactate and Lactylation in Sepsis: A Comprehensive Review.Journal of inflammation research · 2024Review
- Lactate's impact on immune cells in sepsis: unraveling the complex interplay.Frontiers in immunology · 2024Review
- Targeting glycolytic pathway in fibroblast-like synoviocytes for rheumatoid arthritis therapy: challenges and opportunities.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- [Energy metabolism of the immune system : Consequences in chronic inflammation].Zeitschrift fur Rheumatologie · 2023Review
- Glycolysis: an emerging regulator of osteoarthritis.Frontiers in immunology · 2023Review
- Review
- Cellular metabolic adaptations in rheumatoid arthritis and their therapeutic implications.Nature reviews. Rheumatology · 2022Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA dysregulated glucose metabolism in synovial fibroblasts (SF) has been associated with their aggressive phenotype in rheumatoid arthritis (RA). Even though T helper (Th) cells are key effector cells in the propagation and exacerbation of synovitis in RA, little is known about their influence on the metabolism of SF. Thus, this study investigates the effect of Th cells on the glucose metabolism and phenotype of SF and how this is influenced by the blockade of cytokines, janus kinases (JAKs) and glycolysis.
methodsSF from patients with RA or osteoarthritis (OA) were cultured in the presence of a stable glucose isotopomer ([U-
resultsQuiescent RASF produced significantly higher levels of lactate, interleukin (IL)-6 and matrix metalloproteinase (MMP) 3 than OASF. Stimulation by ThCM clearly changed the metabolic profile of both RASF and OASF by inducing a shift towards aerobic glycolysis with strongly increased lactate production together with a rise in IL-6 and MMP3 secretion. Interestingly, chronic stimulation of OASF by ThCM triggered an inflammatory phenotype with significantly increased glycolytic activity compared to unstimulated, singly stimulated or re-stimulated OASF. Finally, in contrast to cytokine-neutralizing biologics, inhibition of JAKs or glycolytic enzymes both significantly reduced lactate production and cytokine secretion by Th cell-stimulated SF.
conclusionsSoluble mediators released by Th cells drive SF towards a glycolytic and pro-inflammatory phenotype. Targeting of JAKs or glycolytic enzymes both potently modulate SF's glucose metabolism and decrease the release of IL-6 and MMP3. Thus, manipulation of glycolytic pathways could represent a new therapeutic strategy to decrease the pro-inflammatory phenotype of SF.
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