ArticleArthritis & rheumatology (Hoboken, N.J.)2015
Semaphorin 4D Contributes to Rheumatoid Arthritis by Inducing Inflammatory Cytokine Production: Pathogenic and Therapeutic Implications.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 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
57 citing papers in PubMed, 97 citations in OpenAlex.
- Spatially Distinct Macrophage Subsets Drive Myofibroblast Heterogeneity and Maladaptive Fibrosis in Lupus Nephritis.bioRxiv : the preprint server for biology · 2026Article
- AP39 suppresses osteoclast differentiation and neural factor expression under inflammatory condition.Journal of orthopaedic surgery and research · 2025Article
- Semaphorin4B is elevated in rheumatoid arthritis and enhances the inflammatory phenotype of macrophages and fibroblast-like synoviocytes.Arthritis research & therapy · 2025Article
- Regulation of Vascular Calcification by M1-Type Macrophage-Derived Semaphorin 4D.International journal of molecular sciences · 2025Article
- Research Advances in the Immunomodulatory Functions of CD100/SEMA4D and Their Roles in Viral Infectious Diseases.International journal of molecular sciences · 2025Review
- Asiaticoside alleviates lipopolysaccharide-induced acute lung injury by blocking Sema4D/CD72 and inhibiting mitochondrial dysfunction in RAW264.7 cell and mice.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- The emerging role of the semaphorin family in cartilage and osteoarthritis.Histochemistry and cell biology · 2024Review
- Review
- Soluble Semaphorin 4D Serum Concentrations Are Elevated in Critically Ill Patients with Liver Cirrhosis and Correlate with Aminotransferases.Diagnostics (Basel, Switzerland) · 2024Article
- Sema4D as a biomarker for Predicting rheumatoid arthritis disease activity.Clinical rheumatology · 2024Article
- Comparison of inflammatory molecular mechanisms between osteoarthritis and rheumatoid arthritis via gene microarrays.Molecular biology research communications · 2024Article
- Antigen-presenting autoreactive B cells activate regulatory T cells and suppress autoimmune arthritis in mice.The Journal of experimental medicine · 2023Article
- Plexin-mediated neuronal development and neuroinflammatory responses in the nervous system.Histology and histopathology · 2023Review
- Association of Immune Semaphorins with COVID-19 Severity and Outcomes.Biomedicines · 2023Article
- Transcriptome-wide association study identifies new susceptibility genes and pathways for spondyloarthritis.Journal of orthopaedic surgery and research · 2023Article
- Protective and Pain-Killer Effects of AMC3, a Novel N-Formyl Peptide Receptors (FPRs) Modulator, in Experimental Models of Rheumatoid Arthritis.Antioxidants (Basel, Switzerland) · 2023Article
- Soluble Sema4D cleaved from osteoclast precursors by TACE suppresses osteoblastogenesis.Journal of cellular and molecular medicine · 2023Article
- The value of serum Sema4D level in predicting the prognosis of patients with acute ST-segment elevation myocardial infarction and with high thrombus burden.BMC cardiovascular disorders · 2023Article
- The value of serum Sema4D level in reflecting the inflammatory state of acute ST-segment elevation myocardial infarction.Journal of thoracic disease · 2023Article
- The Expression of Semaphorin3E in Vagal Ganglion and Lung Tissue Is Related to Airway Hyperresponsiveness in Murine Asthma Model.Journal of immunology research · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveSemaphorin 4D (Sema4D)/CD100 has pleiotropic roles in immune activation, angiogenesis, bone metabolism, and neural development. We undertook this study to investigate the role of Sema4D in rheumatoid arthritis (RA).
methodsSoluble Sema4D (sSema4D) levels in serum and synovial fluid were analyzed by enzyme-linked immunosorbent assay. Cell surface expression and transcripts of Sema4D were analyzed in peripheral blood cells from RA patients, and immunohistochemical staining of Sema4D was performed in RA synovium. Generation of sSema4D was evaluated in an ADAMTS-4-treated monocytic cell line (THP-1 cells). The efficacy of anti-Sema4D antibody was evaluated in mice with collagen-induced arthritis (CIA).
resultsLevels of sSema4D were elevated in both serum and synovial fluid from RA patients, and disease activity markers were correlated with serum sSema4D levels. Sema4D-expressing cells also accumulated in RA synovium. Cell surface levels of Sema4D on CD3+ and CD14+ cells from RA patients were reduced, although levels of Sema4D transcripts were unchanged. In addition, ADAMTS-4 cleaved cell surface Sema4D to generate sSema4D in THP-1 cells. Soluble Sema4D induced tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) production from CD14+ monocytes. IL-6 and TNFα induced ADAMTS-4 expression in synovial cells. Treatment with an anti-Sema4D antibody suppressed arthritis and reduced proinflammatory cytokine production in CIA.
conclusionA positive feedback loop involving sSema4D/IL-6 and TNFα/ADAMTS-4 may contribute to the pathogenesis of RA. The inhibition of arthritis by anti-Sema4D antibody suggests that Sema4D represents a potential therapeutic target for RA.
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.