ArticleImmunity2017
Autocrine Loop Involving IL-6 Family Member LIF, LIF Receptor, and STAT4 Drives Sustained Fibroblast Production of Inflammatory Mediators.
Article in Immunity, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
123 citing papers in PubMed, 2 syntheses or guidelines pooled it, 201 citations in OpenAlex.
- Association of VEGF-116G/A Promoter Polymorphism with Esophageal Cancer Risk: A Case-Control study and an Updated Meta-Analysis on Gastrointestinal Tract Cancers.Asian Pacific journal of cancer prevention : APJCP · 2023Pooled it
- Composition and regulation of the immune microenvironment of salivary gland in Sjögren's syndrome.Frontiers in immunology · 2022Pooled it
- Identification of Prognostic Factors and Regulatory Pathways in Porto-Sinusoidal Vascular Disorder.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Immune-mediated rheumatoid arthritis: from single-cell genomics to new therapies.Nature immunology · 2026Review
- LPS-Induced TNF-α and IL-1 Signaling in Periodontitis: Molecular Mechanisms and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- Interleukin 4-driven loss of stromal LIF signaling affects immune responses and cell-cell adhesion in atopic dermatitis.iScience · 2026Article
- Fibroblasts resistScience advances · 2026Article
- Inflammatory myofibroblasts reprogram neutrophil fate to drive chronic inflammation in peri-implantitis.International journal of oral science · 2026Article
- Early Immune Hypoactivation and Persistent Innate Reprogramming Characterize Chronic Chikungunya Disease.bioRxiv : the preprint server for biology · 2026Article
- Article
- Targeting fibroblasts in immune mediated inflammatory diseases: a cellular basis for cure?Rheumatology (Oxford, England) · 2026Review
- Interleukin-6 fromMicrobiology spectrum · 2026Article
- Article
- Evaluation of Acute Exposure to Combustible and Novel Tobacco Products Using an In Vitro Human Airway Organ Tissue Equivalent Model.Journal of applied toxicology : JAT · 2026Article
- Regulation of basal and tumour necrosis factor α-induced fibroblast gene expression by peptidylarginine deiminase 2.The Journal of physiology · 2026Article
- STAT1 transcriptionally activates CXCL13 to promote cell inflammation and proliferation and inhibit cell apoptosis in rheumatoid arthritis fibroblast-like synoviocytes.Journal of orthopaedic surgery and research · 2026Article
- Article
- Narrative review on the development of multi-target pharmacological agents for the management of rheumatoid arthritis.Inflammopharmacology · 2026Review
- Fibroblasts as Immunological Sentinels in Cutaneous Inflammation: A Review.Journal of clinical medicine · 2026Review
- Piezo1-mediated autophagy promotes immune-inflammatory responses in ankylosing spondylitis.Cell death & disease · 2026Article
63 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Fibroblasts are major contributors to and regulators of inflammation and dominant producers of interleukin-6 (IL-6) in inflammatory diseases like rheumatoid arthritis. Yet, compared to leukocytes, the regulation of inflammatory pathways in fibroblasts is largely unknown. Here, we report that analyses of genes coordinately upregulated with IL-6 pointed to STAT4 and leukemia inhibitory factor (LIF) as potentially linked. Gene silencing revealed that STAT4 was required for IL-6 transcription. STAT4 was recruited to the IL-6 promoter after fibroblast activation, and LIF receptor (LIFR) and STAT4 formed a molecular complex that, together with JAK1 and TYK2 kinases, controlled STAT4 activation. Importantly, a positive feedback loop involving autocrine LIF, LIFR, and STAT4 drove sustained IL-6 transcription. Besides IL-6, this autorine loop also drove the production of other key inflammatory factors including IL-8, granulocyte-colony stimulating factor (G-CSF), IL-33, IL-11, IL-1α, and IL-1β. These findings define the transcriptional regulation of fibroblast-mediated inflammation as distinct from leukocytes.
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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.