ArticleJournal of hepatology2016
Interleukin-15 receptor α on hepatic stellate cells regulates hepatic fibrogenesis in mice.
Article in Journal of hepatology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Autologous macrophage therapy for liver cirrhosis: a phase 2 open-label randomized controlled trial.Nature medicine · 2025Trial
- Astaxanthin Alleviates Bleomycin-Induced Pulmonary Fibrosis in Mice by Suppressing the Fibroblast-to-Myofibroblast Transition and Collagen Deposition.Molecular nutrition & food research · 2026Article
- Development of a High-Throughput Screening Platform and a Pathogenesis Model forInternational journal of molecular sciences · 2025Article
- Taurochenodeoxycholic acid as a sensitive stratification marker for HBV-associated hepatic cirrhosis status has a hepatoprotective effect.Scientific reports · 2025Article
- Hepatocyte senescence and persistent liver injury in Fanconi anemia.Haematologica · 2025Article
- Fibroblast-derived interleukin-11 as a potential biomarker for intestinal fibrostenosis in Crohn's disease.Therapeutic advances in gastroenterology · 2025Article
- Profibrogenic role of IL-15 through IL-15 receptor alpha-mediated trans-presentation in the carbon tetrachloride-induced liver fibrosis model.Frontiers in immunology · 2024Article
- Myokines: Crosstalk and Consequences on Liver Physiopathology.Nutrients · 2023Review
- Pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis.World journal of clinical cases · 2022Review
- Monocytic Myeloid-Derived Suppressor Cells Inhibit Myofibroblastic Differentiation in Mesenchymal Stem Cells Through IL-15 Secretion.Frontiers in cell and developmental biology · 2022Article
- Triptolide increases resistance to bile duct ligation-induced liver injury and fibrosis in mice by inhibiting RELB.Frontiers in nutrition · 2022Article
- Quantifying the progression of non-alcoholic fatty liver disease in human biomimetic liver microphysiology systems with fluorescent protein biosensors.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?International journal of molecular sciences · 2021Article
- Exosomes secreted by palmitic acid-treated hepatocytes promote LX-2 cell activation by transferring miRNA-107.Cell death discovery · 2021Article
- A combination of pirfenidone and TGF-β inhibition mitigates cystic echinococcosis-associated hepatic injury.Parasitology · 2021Article
- Exosomes derived from natural killer cells inhibit hepatic stellate cell activation and liver fibrosis.Human cell · 2020Article
- The signature of HBV-related liver disease in peripheral blood mononuclear cell DNA methylation.Clinical epigenetics · 2020Article
- Human Liver Memory CD8Cell reports · 2020Article
- Salvianolic Acid B Inhibits Activation of Human Primary Hepatic Stellate Cells Through Downregulation of the Myocyte Enhancer Factor 2 Signaling Pathway.Frontiers in pharmacology · 2019Article
- Inhibition of TGF-International journal of cell biology · 2019Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsInterleukin-15 (IL-15) and its high affinity receptor interleukin-15 receptor alpha (IL-15Rα) are widely expressed in immune cells and hepatic resident cells. IL-15 signaling has important functions in homeostasis of natural killer (NK), natural killer T (NKT) and cytotoxic T (CD8(+) T) cells, and in liver regeneration. We hypothesized that IL-15 has a protective role in liver fibrosis progression by maintaining NK cell homeostasis.
methodsFibrosis was induced using two mechanistically distinct models. Congenic bone marrow transplantation was used to evaluate the contribution of IL-15 signaling from various compartments to NK, CD8(+) T and NKT cell homeostasis and fibrogenesis. The gene expression profile of hepatic stellate cell (HSC) from IL-15Rα knockout (IL-15RαKO) mice and wild-type mice were captured using microarray analysis and validated in isolated HSC. Quantitative real-time PCR was used to assess repressors of collagen transcription.
resultsIL-15RαKO mice exhibited more fibrosis in both models. IL-15 signaling from specific types of hepatic cells had divergent roles in maintaining liver NK, CD8(+) T and NKT cells, with a direct and protective role on radio-resistant non-parenchymal cells beyond the control of NK homeostasis. HSCs isolated from IL-15RαKO mice demonstrated upregulation of collagen production. Finally, IL-15RαKO HSC with or without transforming growth factor beta (TGF-β) stimulation exhibited increased expression of fibrosis markers and decreased collagen transcription repressors expression.
conclusionsIL-15Rα signaling has a direct anti-fibrotic effect independent of preserving NK homeostasis. These findings establish a rationale to further explore the anti-fibrotic potential of enhancing IL-15 signaling in HSCs. LAY SUMMARY: We investigated how a cellular protein, Interleukin-15 (IL-15), decreases the amount of scar tissue that is formed upon liver injury. We found that IL-15 and its receptor decrease the amount of scar tissue that is created by specialized liver cells (called stellate cells) and increase the number of a specific subgroup of immune cells (natural killer cells) that are known to eliminate stellate cells. TRANSCRIPT PROFILING ACCESSION NUMBER: GSE45612, GSE 68001 and GSE 25097.
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