ArticleToxicological sciences : an official journal of the Society of Toxicology2019
Hepatocyte-Derived Exosomes Promote Liver Immune Tolerance: Possible Implications for Idiosyncratic Drug-Induced Liver Injury.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- Multifunctional scaffold inspired by hepatocyte exosomes promotes bone regeneration by regulating osteogenic differentiation via PI3K/AKT pathway.Materials today. Bio · 2026Article
- Article
- Molecular regulatory mechanisms and diagnostic potential of dendritic cell-derived exosomes in liver transplantation: from immune tolerance induction to translational challenges.Frontiers in immunology · 2025Review
- Normothermic liver perfusion derived extracellular vesicles have concentration-dependent immunoregulatory properties.Journal of extracellular vesicles · 2024Article
- Seminar: Extracellular Vesicles as Mediators of Environmental Stress in Human Disease.Environmental health perspectives · 2023Article
- Impact of immune tolerance mechanisms on the efficacy of immunotherapy in primary and secondary liver cancers.Translational gastroenterology and hepatology · 2023Review
- The therapeutic potential of exosomes derived from different cell sources in liver diseases.American journal of physiology. Gastrointestinal and liver physiology · 2022Review
- Composition, isolation, identification and function of adipose tissue-derived exosomes.Adipocyte · 2021Review
- Human hepatocyte-derived extracellular vesicles attenuate the carbon tetrachloride-induced acute liver injury in mice.Cell death & disease · 2021Article
- Exosomal microRNAs as diagnostic and therapeutic biomarkers in non-malignant liver diseases.Archives of pharmacal research · 2021Review
- Idiosyncratic Drug-Induced Liver Injury: Mechanistic and Clinical Challenges.International journal of molecular sciences · 2021Review
- Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice.Antioxidants (Basel, Switzerland) · 2021Review
- Review
- Advances on liver cell-derived exosomes in liver diseases.Journal of cellular and molecular medicine · 2021Review
- The Role of Diverse Liver Cells in Liver Transplantation Tolerance.Frontiers in immunology · 2020Review
- Article
- Mechanisms of Immune Tolerance in Liver Transplantation-Crosstalk Between Alloreactive T Cells and Liver Cells With Therapeutic Prospects.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Most idiosyncratic drug-induced liver injury appears to result from an adaptive immune attack on the liver. Recent evidence suggests that the T-cell response may be facilitated by the loss of immune tolerance. In this study, we explored the hypothesis that constitutively released hepatocyte-derived exosomes (HDE) are important for maintaining normal liver immune tolerance. Exosomes were isolated from the conditioned medium of primary human hepatocytes via polymer precipitation. Mock controls were prepared by processing fresh medium that was not hepatocyte exposed with precipitation reagent. THP-1 monocytes were then treated with HDE or an equivalent volume of mock control for 24 h, followed by a 6-h stimulation with LPS. HDE exposure resulted in a significant decrease in the LPS-induced media levels of interleukin-1β and interleukin-8. Gene expression profiling performed in THP-1 cells just prior to LPS-induced stimulation identified a significant decrease among genes associated with innate immune response. MicroRNA (miRNA) profiling was performed on the HDE to identify exosome contents that may drive immune suppression. Many of the predicted mRNA target genes for the most abundant microRNAs in HDE were among the differentially expressed genes in THP-1 cells. Taken together, our data suggest that HDE play a role in maintaining normal liver immune tolerance. Future experiments will explore the possibility that drugs causing idiosyncratic liver injury promote the loss of homeostatic HDE signaling.
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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.