ArticleArthritis & rheumatology (Hoboken, N.J.)2021
Interleukin-34 Reprograms Glycolytic and Osteoclastic Rheumatoid Arthritis Macrophages via Syndecan 1 and Macrophage Colony-Stimulating Factor Receptor.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 42 citations in OpenAlex.
- BCAT2 links branched-chain amino acids metabolism to interferon signaling to sustain macrophage inflammation.Nature immunology · 2026Article
- Airway macrophage specific glycocalyx expression and remodeling following viral infection.Matrix biology : journal of the International Society for Matrix Biology · 2026Article
- IL-34 Regulates Macrophage Polarization and Bone Defect Healing in Aged Mice.International journal of molecular sciences · 2026Article
- The emerging role of lactate in skeletal homeostasis and disorders: Integrated mechanisms and translational opportunities.Journal of orthopaedic translation · 2026Review
- A CD138+ tumor-associated macrophage/Siglec-F+ neutrophil feed-forward loop promotes immune evasion in pancreatic cancer.The Journal of clinical investigation · 2026Article
- Tofacitinib repairs inflammation and mitochondrial dysregulation in GM-CSF-reprogrammed RA macrophages.Cellular & molecular immunology · 2026Article
- Supplemental exposure to polystyrene nanoplastics synergistically amplifies calcium oxalate crystal-induced injury to renal tubular epithelium, accelerating the formation of calcium oxalate kidney stones.Particle and fibre toxicology · 2026Article
- Immunometabolic dysregulation in autoimmune rheumatic diseases: the central role of glycolytic reprogramming in pathogenesis and traditional Chinese medicine therapy.Frontiers in immunology · 2026Review
- Roles of IL-34 in neurological diseases: neuroprotection, inflammatory regulation, and myeloid plasticity.Frontiers in immunology · 2026Review
- GRK2-mediated phosphorylation and de-succinylation of PKM2 reduce macrophage glycolysis in rheumatoid arthritis.Acta pharmacologica Sinica · 2025Article
- The Role of Cytokines in Orthodontic Tooth Movement.International journal of molecular sciences · 2025Review
- [Bioinformatics analysis of oxidative stress and immune infiltration in rheumatoid arthritis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- IL-34 aggravates myocardial ischemia-reperfusion injury by upregulating the HMGB1-IL-17A-IL-6 axis through the JAK signaling pathway.PloS one · 2025Article
- The Role and Mechanism of Protein Post‑Translational Modification in Rheumatoid Arthritis.Journal of inflammation research · 2025Review
- Association between triglyceride-glucose index and activities of daily living disability among middle-aged and older patients with arthritis: longitudinal evidence from CHARLS.Frontiers in medicine · 2025Article
- Crossing the metabolic homeostasis divide: panoramic decoding of therapeutic targets for metabolic-inflammatory crosstalk in rheumatoid arthritis.Frontiers in immunology · 2025Review
- Metabolic reprogramming: the central mechanism driving inflammatory polarization in rheumatoid arthritis and the regulatory role of traditional Chinese medicine.Frontiers in immunology · 2025Review
- Bromodomain-Containing 4 Is a Positive Regulator of Interleukin-34 Production in the Gut.Cells · 2024Article
- Triglyceride-glucose index in the prediction of new-onset arthritis in the general population aged over 45: the first longitudinal evidence from CHARLS.Lipids in health and disease · 2024Article
- IL-34 attenuates acute T cell-mediated rejection following renal transplantation by upregulating M2 macrophages polarization.Heliyon · 2024Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveIn rheumatoid arthritis (RA), elevated serum interleukin-34 (IL-34) levels are linked with increased disease severity. IL-34 binds to 2 receptors, macrophage colony-stimulating factor receptor (M-CSFR) and syndecan 1, which are coexpressed in RA macrophages. Expression of both IL-34 and syndecan 1 is strikingly elevated in the RA synovium, yet their mechanisms of action remain undefined. This study was undertaken to investigate the mechanism of action of IL-34 in RA.
methodsTo characterize the significance of IL-34 in immunometabolism, its mechanism of action was elucidated in joint macrophages, fibroblasts, and T effector cells using RA and preclinical models.
resultsIntriguingly, syndecan 1 activated IL-34-induced M-CSFR phosphorylation and reprogrammed RA naive cells into distinctive CD14+CD86+GLUT1+ M34 macrophages that expressed elevated levels of IL-1β, CXCL8, and CCL2. In murine M34 macrophages, the inflammatory phenotype was accompanied by potentiated glycolytic activity, exhibited by transcriptional up-regulation of GLUT1, c-Myc, and hypoxia-inducible factor 1α (HIF-1α) and amplified pyruvate and l-lactate secretion. Local expression of IL-34 provoked arthritis by expanding the glycolytic F4/80-positive, inducible nitric oxide synthase (iNOS)-positive macrophage population, which in turn attracted fibroblasts and polarized Th1/Th17 cells. The cross-talk between murine M34 macrophages and Th1/Th17 cells broadened the inflammatory and metabolic phenotypes, resulting in the expansion of IL-34 pathogenicity. Consequently, IL-34-instigated joint inflammation was alleviated in RAG
conclusionIL-34 is a novel endogenous factor that remodels hypermetabolic M34 macrophages and facilitates their cross-regulation with T effector cells to advance inflammatory bone destruction in RA.
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