ArticleThe Journal of experimental medicine2016
Anti-TNF drives regulatory T cell expansion by paradoxically promoting membrane TNF-TNF-RII binding in rheumatoid arthritis.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 2 of them syntheses that pooled it.
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Who cites it
103 citing papers in PubMed, 2 syntheses or guidelines pooled it, 173 citations in OpenAlex.
- Systematic Review: Monoclonal Antibody-Induced Subacute Cutaneous Lupus Erythematosus.Drugs in R&D · 2020Pooled it
- The Proportion of Regulatory T Cells in Patients with Ankylosing Spondylitis: A Meta-Analysis.Journal of immunology research · 2019Pooled it
- Monocyte/Macrophage Abnormalities Specific to Rheumatoid Arthritis Are Linked to miR-155 and Are Differentially Modulated by Different TNF Inhibitors.Journal of immunology (Baltimore, Md. : 1950) · 2019Trial
- Current landscape of drug induced retinal vasculitis.Journal of ophthalmic inflammation and infection · 2026Review
- Multiple Modes of Action of Anti-TNF-α Antibodies for Inflammatory Bowel Diseases Beyond TNF-α Neutralization.Antibodies (Basel, Switzerland) · 2026Review
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- Promising TNF-α inhibitors: Targeting pathogenic TNF-α/TNFR signaling to restore Th17/Treg balance in rheumatoid arthritis.Journal of pharmaceutical analysis · 2026Review
- TRIP13 promotes the expansion and immunosuppression of CD4Cell death & disease · 2026Article
- Failed resolution as a mechanistic basis of difficult-to-treat rheumatoid arthritis: stromal-myeloid crosstalk in the synovium and emerging resolution-restoring therapies.Frontiers in immunology · 2026Review
- Regulatory T cells in human pregnancy: mechanisms, dysregulation, and therapeutic perspectives.Frontiers in immunology · 2026Review
- TNF-α blockade with adalimumab restores bone metabolism in rheumatoid arthritis by regulating cytokines and inflammatory cell infiltration.Frontiers in immunology · 2026Article
- The prevalence and potential associations of anti-drug antibodies against adalimumab in patients with non-infectious uveitis: a cross-sectional study.Journal of ophthalmic inflammation and infection · 2025Article
- TNF Production or TNFR2 Expression Characterize Distinct States of Regulatory T Cells that Cooperate in Treg Expansion in Cancer and Chronic Inflammation.European journal of immunology · 2025Article
- Multi-omics analysis of tumor necrosis factor superfamily 4 reveals its prognostic value with T cell exhaustion feature in cancer.Discover oncology · 2025Article
- The 'TNature reviews. Rheumatology · 2025Review
- Cytokine Profile in Predicting the Effectiveness of Advanced Therapy for Ulcerative Colitis: A Narrative Review.Biomedicines · 2024Review
- Immunological factors linked to geographical variation in vaccine responses.Nature reviews. Immunology · 2024Review
- Tregs from human blood differentiate into nonlymphoid tissue-resident effector cells upon TNFR2 costimulation.JCI insight · 2024Article
- A personalized network framework reveals predictive axis of anti-TNF response across diseases.Cell reports. Medicine · 2024Article
- Identification of a transcription factor network regulating anti-TNF mediatedDiscovery immunology · 2024Article
43 more citing papers are in PubMed but not listed here.
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2 authors at 1 institution in 1 country.
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Abstract
The interplay between inflammatory and regulatory pathways orchestrates an effective immune response that provides protection from pathogens while limiting injury to host tissue. Tumor necrosis factor (TNF) is a pivotal inflammatory cytokine, but there is conflicting evidence as to whether it boosts or inhibits regulatory T cells (T reg cells). In this study, we show that the therapeutic anti-TNF antibody adalimumab, but not the soluble TNF receptor etanercept, paradoxically promoted the interaction between monocytes and T reg cells isolated from patients with rheumatoid arthritis (RA). Adalimumab bound to monocyte membrane TNF from RA patients and unexpectedly enhanced its expression and its binding to TNF-RII expressed on T reg cells. As a consequence, adalimumab expanded functional Foxp3(+) T reg cells equipped to suppress Th17 cells through an IL-2/STAT5-dependent mechanism. Our data not only highlight the beneficial effect of membrane TNF on T reg cell numbers during chronic inflammation, but in addition reveal how a therapeutic antibody that is thought to act by simply blocking its target can enhance the regulatory properties of this proinflammatory cytokine.
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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.