Observational studyHepatology (Baltimore, Md.)2021
Myeloid-Cell-Specific IL-6 Signaling Promotes MicroRNA-223-Enriched Exosome Production to Attenuate NAFLD-Associated Fibrosis.
Observational study in Hepatology (Baltimore, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 3 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
127 citing papers in PubMed, 3 syntheses or guidelines pooled it, 210 citations in OpenAlex.
- The use of circulating miRNAs for the diagnosis, prognosis, and personalized treatment of MASLD.Journal of physiology and biochemistry · 2025Pooled it
- Systematic review of extracellular vesicle-derived microRNAs involved in organ fibrosis: implications for arthrofibrosis therapy.Journal of translational medicine · 2025Pooled it
- Association of Inflammatory Cytokines With Non-Alcoholic Fatty Liver Disease.Frontiers in immunology · 2022Pooled it
- IL-6/STAT3-Mediated miR-181a-5p in Bone Marrow-Derived Mesenchymal Stem Cells Regulates Th17/Treg Balance in Experimental Periodontitis.International dental journal · 2026Article
- Unifying and unique roles of non-coding RNA biomarkers in liver and heart fibrosis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Review
- Bixin and Montelukast Combination Mitigates the Progression of MASLD to Cytokine-Driven Inflammatory Stress in an In Vitro Fluid-Dynamic Model.ACS omega · 2026Article
- Macrophage Notch1 drives hepatocyte ferroptosis via the exosomal miR-142a-3p/TIPE2 axis to promote MASH progression.Cell & bioscience · 2026Article
- mRNA-laden LNP-enabled in situ CAR-macrophage alleviates liver fibrosis via inhibiting activated HSCs and modulating the immune microenvironment.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Non-coding RNA networks in metabolic dysfunction-associated steatotic liver disease: Mechanisms and therapeutic perspectives.Liver research (Beijing, China) · 2026Review
- Extracellular Vesicles in Liver Disease: Redefining Diagnostic and Therapeutic Strategies.International journal of stem cells · 2026Review
- The pathogenesis of liver fibrosis in Wilson's disease: hepatocyte injury and regulation mediated by copper metabolism dysregulation.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Extracellular Vesicles: Orchestrators of Intrahepatic and Systemic Crosstalk in Metabolic Dysfunction-Associated Steatotic Liver Disease.Pharmaceutics · 2026Review
- MicroRNAs as Key Regulators in the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Bioinformatics Analysis.Biomedicines · 2026Article
- Nanotherapeutic Strategies for MASLD: From Pathological Mechanisms to Targeted Delivery Systems.International journal of nanomedicine · 2026Review
- Role of miRNA signalling in the pathogenesis of MASLD.Frontiers in pharmacology · 2026Review
- Refining MASLD Phenotypes: Clinical, Metabolic, and Elastographic Differences Between Adipose Tissue Dysfunction and Obesity-Driven Disease.Nutrients · 2025Observational
- Epigenetic Mechanisms in Autoimmune Thyroid Diseases: Bridging Research and Clinical Applications.International journal of molecular sciences · 2025Review
- Lipid profile and non-alcoholic fatty liver disease detected by ultrasonography: is systemic inflammation a necessary mediator?Annals of medicine · 2025Article
- Hic-5 deficiency attenuates MAFLD by inhibiting neutrophils migration via the CXCL1-CXCR2 axis.Journal of gastroenterology · 2025Article
- Bone marrow mesenchymal stem cell-derived exosomes attenuate hepatic stellate cell activation through miR-223-3p-mediated mitophagy.BMC medical genomics · 2025Article
67 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND ANDS
aimsNAFLD is associated with elevation of many cytokines, particularly IL-6; however, the role of IL-6 in NAFLD remains obscure. The aim of this study was to examine how myeloid-specific IL-6 signaling affects NAFLD by the regulation of antifibrotic microRNA-223 (miR-223) in myeloid cells. APPROACH AND
resultsPatients with NAFLD or NASH and healthy controls were recruited, and serum IL-6 and soluble IL-6 receptor α (sIL-6Rα) were measured. Compared to controls, serum IL-6 and sIL-6Rα levels were elevated in NAFLD/NASH patients. IL-6 levels correlated positively with the number of circulating leukocytes and monocytes. The role of IL-6 in NAFLD was investigated in Il6 knockout (KO) and Il6 receptor A (Il6ra) conditional KO mice after high-fat diet (HFD) feeding. HFD-fed Il6 KO mice had worse liver injury and fibrosis, but less inflammation, compared to wild-type mice. Hepatocyte-specific Il6ra KO mice had more steatosis and liver injury, whereas myeloid-specific Il6ra KO mice had a lower number of hepatic infiltrating macrophages (IMs) and neutrophils with increased cell death of these cells, but greater liver fibrosis (LF), than WT mice. Mechanistically, the increased LF in HFD-fed, myeloid-specific Il6ra KO mice was attributable to the reduction of antifibrotic miR-223 and subsequent up-regulation of the miR-223 target gene, transcriptional activator with PDZ-binding motif (TAZ), a well-known factor to promote NASH fibrosis. In vitro, IL-6 treatment up-regulated exosome biogenesis-related genes and subsequently promoted macrophages to release miR-223-enriched exosomes that were able to reduce profibrotic TAZ expression in hepatocytes by exosomal transfer. Finally, serum IL-6 and miR-223 levels were elevated and correlated with each other in NAFLD patients.
conclusionsMyeloid-specific IL-6 signaling inhibits LF through exosomal transfer of antifibrotic miR-223 into hepatocytes, providing therapeutic targets for NAFLD therapy.
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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.