ArticleJCI insight2018
Mesenchymal TNFR2 promotes the development of polyarthritis and comorbid heart valve stenosis.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
15 citing papers in PubMed, 28 citations in OpenAlex.
- Differential Neutrophil and Eosinophil Infiltrations in the Sub-Lining Compartment of Rheumatoid Versus Osteoarthritic Synovium.Mediterranean journal of rheumatology · 2025Article
- Analysis of Cardiovascular Risk Factors in Patients with Psoriasis: A Cross-Sectional Study.Mediterranean journal of rheumatology · 2025Article
- Article
- Distinct fibroblast functions associated with fibrotic and immune-mediated inflammatory diseases and their implications for therapeutic development.F1000Research · 2024Review
- Fir(e)ing the Rhythm: Inflammatory Cytokines and Cardiac Arrhythmias.JACC. Basic to translational science · 2023Review
- The second decade of anti-TNF-a therapy in clinical practice: new lessons and future directions in the COVID-19 era.Rheumatology international · 2022Review
- Harnessing murine models of Crohn's disease ileitis to advance concepts of pathophysiology and treatment.Mucosal immunology · 2022Review
- Fundamentally different roles of neuronal TNF receptors in CNS pathology: TNFR1 and IKKβ promote microglial responses and tissue injury in demyelination while TNFR2 protects against excitotoxicity in mice.Journal of neuroinflammation · 2021Article
- Tumor necrosis factor alpha and interleukin 1 beta suppress myofibroblast activation via nuclear factor kappa B signaling in 3D-cultured mitral valve interstitial cells.Acta biomaterialia · 2021Article
- Contrasting contributions of TNF from distinct cellular sources in arthritis.Annals of the rheumatic diseases · 2020Article
- Ectopic bone formation and systemic bone loss in a transmembrane TNF-driven model of human spondyloarthritis.Arthritis research & therapy · 2020Article
- Tumor Necrosis Factor Induces Obliterative Pulmonary Vascular Disease in a Novel Model of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.Arthritis & rheumatology (Hoboken, N.J.) · 2020Article
- Cardiac phenotype in mouse models of systemic autoimmunity.Disease models & mechanisms · 2019Review
- The circadian regulator Bmal1 in joint mesenchymal cells regulates both joint development and inflammatory arthritis.Arthritis research & therapy · 2019Article
- Transgenic mice overexpressing human TNF-α experience early onset spontaneous intervertebral disc herniation in the absence of overt degeneration.Cell death & disease · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesenchymal TNF signaling is etiopathogenic for inflammatory diseases such as rheumatoid arthritis and spondyloarthritis (SpA). The role of Tnfr1 in arthritis has been documented; however, Tnfr2 functions are unknown. Here, we investigate the mesenchymal-specific role of Tnfr2 in the TnfΔARE mouse model of SpA in arthritis and heart valve stenosis comorbidity by cell-specific, Col6a1-cre-driven gene targeting. We find that TNF/Tnfr2 signaling in resident synovial fibroblasts (SFs) and valvular interstitial cells (VICs) is detrimental for both pathologies, pointing to common cellular mechanisms. In contrast, systemic Tnfr2 provides protective signaling, since its complete deletion leads to severe deterioration of both pathologies. SFs and VICs lacking Tnfr2 fail to acquire pathogenic activated phenotypes and display increased expression of antiinflammatory cytokines associated with decreased Akt signaling. Comparative RNA sequencing experiments showed that the majority of the deregulated pathways in TnfΔARE mesenchymal-origin SFs and VICs, including proliferation, inflammation, migration, and disease-specific genes, are regulated by Tnfr2; thus, in its absence, they are maintained in a quiescent nonpathogenic state. Our data indicate a pleiotropy of Tnfr2 functions, with mesenchymal Tnfr2 driving cell activation and arthritis/valve stenosis pathogenesis only in the presence of systemic Tnfr2, whereas nonmesenchymal Tnfr2 overcomes this function, providing protective signals and, thus, containing both pathologies.
Indexed as
Identifiers
What OpenQuestion holds
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.