ArticleArthritis and rheumatism2012
The interferon signature and STAT1 expression in rheumatoid arthritis synovial fluid macrophages are induced by tumor necrosis factor α and counter-regulated by the synovial fluid microenvironment.
Article in Arthritis and rheumatism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- Modulation of TNF-induced macrophage polarization by synovial fibroblasts.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- An iguratimod prodrug reduces RA-FLS invasiveness by disrupting STAT1-C3-TNFα-mediated crosstalk between fibroblast-like synoviocytes and macrophages.Journal of orthopaedic translation · 2026Article
- BCAT2 links branched-chain amino acids metabolism to interferon signaling to sustain macrophage inflammation.Nature immunology · 2026Article
- Graphical Representation of Cell Count in Native Joint Aspirates.Diagnostics (Basel, Switzerland) · 2026Article
- Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveal macrophage subpopulation characteristics and the role of STAT1 in rheumatoid arthritis.Journal of translational medicine · 2025Article
- Innate immune memory in inflammatory arthritis.Nature reviews. Rheumatology · 2023Review
- Regulation of type I interferon signature by VGLL3 in the fibroblast-like synoviocytes of rheumatoid arthritis patients via targeting the Hippo pathway.Arthritis research & therapy · 2022Article
- Repolarization of Unbalanced Macrophages: Unmet Medical Need in Chronic Inflammation and Cancer.International journal of molecular sciences · 2022Review
- Hepatic damage caused by long-term high cholesterol intake induces a dysfunctional restorative macrophage population in experimental NASH.Frontiers in immunology · 2022Article
- Autoinflammation and autoimmunity across rheumatic and musculoskeletal diseases.Nature reviews. Rheumatology · 2021Review
- Type I Interferons in Systemic Autoimmune Diseases: Distinguishing Between Afferent and Efferent Functions for Precision Medicine and Individualized Treatment.Frontiers in pharmacology · 2021Review
- Article
- Promotion of macrophage activation by Tie2 in the context of the inflamed synovia of rheumatoid arthritis and psoriatic arthritis patients.Rheumatology (Oxford, England) · 2020Article
- Macrophage depletion with clodronate-containing liposomes affects the incidence and development of rheumatoid arthritis.Zeitschrift fur Rheumatologie · 2019Article
- IL‑1β increases the expression of inflammatory factors in synovial fluid‑derived fibroblast‑like synoviocytes via activation of the NF‑κB‑mediated ERK‑STAT1 signaling pathway.Molecular medicine reports · 2019Article
- HBEGFScience translational medicine · 2019Article
- Gene Expression Profiling in Behcet's Disease Indicates an Autoimmune Component in the Pathogenesis of the Disease and Opens New Avenues for Targeted Therapy.Journal of immunology research · 2018Article
- Immune Response toJournal of immunology research · 2018Article
- MicroRNA Expression Profiling in Behçet's Disease.Journal of immunology research · 2018Article
- IRF4 and IRGs Delineate Clinically Relevant Gene Expression Signatures in Systemic Lupus Erythematosus and Rheumatoid Arthritis.Frontiers in immunology · 2018Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveType I interferons (IFNs) have emerged as potential activators of the IFN signature and elevated STAT-1 expression in rheumatoid arthritis (RA) synovium, but mechanisms that induce synovial IFN expression are unknown. Recently, tumor necrosis factor α (TNFα) was shown to induce a delayed IFN response in macrophages. We undertook this study to test whether TNFα, classically thought to activate inflammatory NF-κB target genes in RA, also contributes to the "IFN signature" in RA synovial macrophages.
methodsSynovial fluid (SF) macrophages purified from 24 patients with RA and 18 patients with spondylarthritides (SpA) were lysed immediately after isolation or were cultured ex vivo in the absence or presence of blockade of endogenous type I IFN or TNFα. Expression of IFN-inducible target genes was measured by quantitative reverse transcription-polymerase chain reaction, and expression of their corresponding proteins was measured by enzyme-linked immunosorbent assay.
resultsExpression of an IFN signature and STAT1 in RA synovial macrophages was suppressed when type I IFNs or TNFα were blocked, whereas TNFα blockade did not affect expression of IFN response genes or STAT1 in SpA synovial macrophages. RA SF suppressed the IFN signature in RA synovial macrophages and in TNFα-, IFNα-, and IFNβ-stimulated control macrophages. Type I IFNs suppressed expression of IL8 and MMP9 in RA synovial macrophages and in TNFα-stimulated control macrophages.
conclusionOur findings identify a new function of TNFα in RA synovitis by implicating TNFα as a major inducer of the RA synovial IFN response. The results suggest that the expression of IFN response genes in RA synovium is regulated by interplay between TNFα and opposing homeostatic factors expressed in the synovial microenvironment.
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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.