ArticleJournal of immunology (Baltimore, Md. : 1950)2013
A synthetic TLR3 ligand mitigates profibrotic fibroblast responses by inducing autocrine IFN signaling.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 60 citations in OpenAlex.
- Engineering nanoparticle surface chemistry for antigen-presenting cell targeting improves specificity and safety of TLR3 agonist cancer immunotherapy.bioRxiv : the preprint server for biology · 2026Article
- Innate immune sensing of alphavirus chikungunya: balancing antiviral defense and pathogenesis.Frontiers in immunology · 2026Review
- Polyinosinic:polycytidylic acid causes epithelial-mesenchymal transition via BAFF expression in Beas-2B human bronchial epithelial cells.International journal of medical sciences · 2026Article
- The differential impact of HNRNPA1 isoforms on gene expression and their relevance to dsRNA-mediated innate immune response.Scientific reports · 2025Article
- Single-Cell Transcriptomics Identified Fibrosis-Activated Valve Interstitial Cells Involved in Functional Tricuspid Regurgitation.JACC. Asia · 2025Article
- Research progress and strategies for vaccines and targeted drugs against highly virulent porcine epidemic diarrhea virus.Frontiers in microbiology · 2025Review
- Toll-like receptor agonists as cancer vaccine adjuvants.Human vaccines & immunotherapeutics · 2024Review
- Extracellular vesicles secreted by equine adipose mesenchymal stem cells preconditioned with transforming growth factor β-1 are enriched in anti-fibrotic miRNAs and inhibit the expression of fibrotic genes in an in vitro system of endometrial stromal cells fibrosis.The veterinary quarterly · 2024Article
- Profiling of Toll-like Receptors and Related Signaling Mediators in the Pathogenesis of Morphea.Dermatology practical & conceptual · 2024Article
- Immunity and Coagulation in COVID-19.International journal of molecular sciences · 2024Review
- Anti-Th/To Antibodies in Scleroderma: Good Prognosis or Serious Concern?Journal of clinical medicine · 2024Review
- TLRs: Innate Immune Sentries against SARS-CoV-2 Infection.International journal of molecular sciences · 2023Review
- Molecular Mechanisms Behind the Role of Plasmacytoid Dendritic Cells in Systemic Sclerosis.Biology · 2023Review
- Plasma extracellular vesicle messenger RNA profiling identifies prognostic EV signature for non-invasive risk stratification for survival prediction of patients with pancreatic ductal adenocarcinoma.Journal of hematology & oncology · 2023Article
- Prevention of bleomycin-induced pulmonary fibrosis by a RANKL peptide in mice.Scientific reports · 2022Article
- Article
- Deficiency of Formyl Peptide Receptor 2 Retards Hair Regeneration by Modulating the Activation of Hair Follicle Stem Cells and Dermal Papilla Cells in Mice.Development & reproduction · 2021Article
- Upcoming treatments for morphea.Immunity, inflammation and disease · 2021Review
- The interplay of DAMPs, TLR4, and proinflammatory cytokines in pulmonary fibrosis.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Toll-like receptor 3 (TLR3) regulation mechanisms and roles in antiviral innate immune responses.Journal of Zhejiang University. Science. B · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Activation of TLR3 by exogenous microbial ligands or endogenous injury-associated ligands leads to production of type I IFN. Scleroderma patients with progressive skin fibrosis display an IFN-regulated gene signature, implicating TLR3 signaling in the disease. In this study, we show that TLR3 expression was detected on foreskin, adult skin, and lung fibroblasts, and TLR3 levels were significantly elevated in a subset of scleroderma skin biopsies. In explanted skin and lung fibroblasts, the synthetic TLR3 ligand polyinosinic-polycytidylic acid (poly(I:C)), a dsRNA analog, caused dose- and time-dependent stimulation of IFN-β production and generation of an IFN-response gene signature that was accompanied by substantial downregulation of collagen and α-smooth muscle actin gene expression. Furthermore, poly(I:C) abrogated TGF-β-induced fibrotic responses and blocked canonical Smad signaling via upregulation of inhibitory Smad7. Surprisingly, the inhibitory effects of poly(I:C) in fibroblasts were independent of TLR3 and were mediated by the cytosolic receptors retinoic acid-inducible gene 1 and melanoma differentiation-associated gene 5, and involved signaling via the IFN receptor. Taken together, these results demonstrate that induction of a fibroblast IFN response gene signature triggered by dsRNA is associated with potent TLR3-independent anti-fibrotic effects. The characteristic IFN response gene signature seen in scleroderma lesions might therefore signify a tissue-autonomous protective attempt to restrict fibroblast activation during injury.
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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.