ArticleNature communications2024
TNF inhibitors target a mevalonate metabolite/TRPM2/calcium signaling axis in neutrophils to dampen vasculitis in Behçet's disease.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.
What it found
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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
9 citing papers in PubMed.
- Transient receptor potential vanilloid 2 functions as a directional driver for hepoxilin AScience advances · 2026Article
- Comparative efficacy and safety of tofacitinib versus adalimumab in patients with Behçet's uveitis: a real-world retrospective study.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Article
- Pregnancy Loss History Is Associated with Systemic Involvement and Disease Activity in Women with Behçet's Disease: A Retrospective Cohort Study.Diagnostics (Basel, Switzerland) · 2026Article
- Article
- Research on the process of synergistic degradation of corn straw by probiotics-enzymes based on microbiome and metabolomics.BMC microbiology · 2026Article
- Advances of Intraocular Fluid for the Application and Treatment of Uveitis.Clinical ophthalmology (Auckland, N.Z.) · 2026Review
- The emerging role of neutrophil extracellular traps in autoimmune and autoinflammatory diseases.MedComm · 2025Review
- Neutrophils: emerging perspectives on the pathogenesis of oral mucosal diseases.Frontiers in cellular and infection microbiology · 2025Review
- Recent Advances of Trained immunity in Macrophages.International journal of biological sciences · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
26 authors.
Funding
Abstract
TNF inhibitors have been used to treat autoimmune and autoinflammatory diseases. Here we report an unexpected mechanism underlying the therapeutic effects of TNF inhibitors in Behçet's disease (BD), an autoimmune inflammatory disorder. Using serum metabolomics and peripheral immunocyte transcriptomics, we find that polymorphonuclear neutrophil (PMN) from patients with BD (BD-PMN) has dysregulated mevalonate pathway and subsequently increased farnesyl pyrophosphate (FPP) levels. Mechanistically, FPP induces TRPM2-calcium signaling for neutrophil extracellular trap (NET) and proinflammatory cytokine productions, leading to vascular endothelial inflammation and damage. TNF, but not IL-1β, IL-6, IL-18, or IFN-γ, upregulates TRPM2 expression on BD-PMN, while TNF inhibitors have opposite effects. Results from mice with PMN-specific FPP synthetase or TRPM2 deficiency show reduced experimental vasculitis. Meanwhile, analyses of public datasets correlate increased TRPM2 expressions with the clinical benefits of TNF inhibitors. Our results thus implicate FPP-TRPM2-TNF/NETs feedback loops for inflammation aggravation, and novel insights for TNF inhibitor therapies on BD.
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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 Socratic graph.