ArticleJournal of immunology (Baltimore, Md. : 1950)2014
IL-17A enhances the expression of profibrotic genes through upregulation of the TGF-β receptor on hepatic stellate cells in a JNK-dependent manner.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 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
98 citing papers in PubMed, 141 citations in OpenAlex.
- Collaborative functionality between three types of inflammation in idiopathic pulmonary fibrosis.Nature immunology · 2026Review
- Unleashing innovative cross-organ fibrosis therapies by harnessing the omics revolution.JCI insight · 2026Review
- Hepatic stellate cell enriched Asporin drives liver fibrosis by stabilizing ERH to promote IL-17/MAPK11 signaling.Acta pharmaceutica Sinica. B · 2026Article
- Impact of Gene Polymorphism rs2275913 and Serum IL-17A Levels on Liver Fibrosis Severity Across the Natural History of Chronic Hepatitis B in Indonesia.Diseases (Basel, Switzerland) · 2026Article
- Clonorchis sinensis excretory secretory products promote hepatic fibrosis through stimulating biliary epithelium to secrete IL-17A.PLoS neglected tropical diseases · 2026Article
- Review
- Type 2 lymphocytes restrict type 3 lymphocytes during liver fibrosis and colocalize in fibroblast niches.Science advances · 2026Article
- The Double-Edged Sword of Type 17 Immunity in Wound Healing and Skin Barrier Repair: Microenvironment-Driven Functional Plasticity.Biomolecules · 2026Review
- WNT3a induces external anal sphincter fibrosis and dysfunction in rabbits.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- TRIM21enhances IL-17A signaling and drives autoimmune myocarditis by promoting TRAF3 lysosomaldegradation in cardiac fibroblasts.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Effect of free fatty acids on TGF-β1 mediated fibrogenesis in hepatic stellate cells.Molecular metabolism · 2026Article
- Hepatic Safety of IL-17 Inhibitors in Psoriasis and Psoriatic Arthritis: A 12-Month Retrospective Cohort Evaluation Using the FIB-4 Index.Dermatology practical & conceptual · 2026Article
- Glucolipid Metabolic Disorders andInternational journal of endocrinology · 2026Review
- Immune System and Hepatic Stellate Cells' Crosstalk in Liver Fibrosis: Pathways and Therapeutic Potential.Journal of immunology research · 2026Review
- Article
- Dual roles of T cells in metabolic dysfunction-associated steatohepatitis pathogenesis and liver fibrosis: From inflammation to therapeutic targets.Hepatology communications · 2025Review
- Role of IL-17 cytokines in tubal fibrosis and infertility due to salpingitis.Molecular biology reports · 2025Review
- Myeloid cells in chronic liver inflammation.Cellular & molecular immunology · 2025Review
- Fibrosis in Immune-Mediated and Autoimmune Disorders.Journal of clinical medicine · 2025Review
- Exploring the Therapeutic Potential of TGF-β Inhibitors for Liver Fibrosis: Targeting Multiple Signaling Pathways.Journal of clinical and translational hepatology · 2025Review
38 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
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Activation of hepatic stellate cells (HSCs) is a key event in the initiation of liver fibrosis, characterized by enhanced extracellular matrix production and altered degradation. Activation of HSCs can be modulated by cytokines produced by immune cells. Recent reports have implicated the proinflammatory cytokine IL-17A in liver fibrosis progression. We hypothesized that IL-17A may enhance activation of HSCs and induction of the fibrogenic signals in these cells. The human HSC line LX2 and primary human HSCs were stimulated with increasing doses of IL-17A and compared with TGF-β- and PBS-treated cells as positive and negative controls, respectively. IL-17A alone did not induce activation of HSCs. However, IL-17A sensitized HSCs to the action of suboptimal doses of TGF-β as confirmed by strong induction of α-smooth muscle actin, collagen type I (COL1A1), and tissue inhibitor of matrix metalloproteinase I gene expression and protein production. IL-17A specifically upregulated the cell surface expression of TGF-βRII following stimulation. Pretreatment of HSCs with IL-17A enhanced signaling through TGF-βRII as observed by increased phosphorylation of SMAD2/3 in response to stimulation with suboptimal doses of TGF-β. This enhanced TGF-β response of HSCs induced by IL-17A was JNK-dependent. Our results suggest a novel profibrotic function for IL-17A by enhancing the response of HSCs to TGF-β through activation of the JNK pathway. IL-17A acts through upregulation and stabilization of TGF-βRII, leading to increased SMAD2/3 signaling. These findings represent a novel example of cooperative signaling between an immune cytokine and a fibrogenic receptor.
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.