ArticleHepatology (Baltimore, Md.)2019
Exosomal Transport of Hepatocyte-Derived Drug-Modified Proteins to the Immune System.
Article in Hepatology (Baltimore, Md.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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
21 citing papers in PubMed, 43 citations in OpenAlex.
- Profiling the pancreatic cancer secretome with metabolic glycoengineering.The Journal of biological chemistry · 2026Article
- HLA-A*02:01 Presents Penicillin-Modified Cysteinylated Peptides for T Cell Recognition.Allergy · 2025Article
- Proteomic profile of the antibody diversity in circulating extracellular vesicles of lung adenocarcinoma.Scientific reports · 2024Article
- Selective HLA Class II Allele-Restricted Activation of Atabecestat Metabolite-Specific Human T-Cells.Chemical research in toxicology · 2024Article
- Extracellular vesicles (EVs)' journey in recipient cells: from recognition to cargo release.Journal of Zhejiang University. Science. B · 2024Review
- Roadmap to DILI research in Europe. A proposal from COST action ProEuroDILINet.Pharmacological research · 2024Article
- A blinded in vitro analysis of the intrinsic immunogenicity of hepatotoxic drugs: implications for preclinical risk assessment.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Differential intracellular trafficking of extracellular vesicles in microglia and astrocytes.Cellular and molecular life sciences : CMLS · 2023Article
- Immuno-inflammatoryFrontiers in immunology · 2023Article
- Plasma-derived exosomal immunoglobulins IGHV4-4 and IGLV1-40 as new non-small cell lung cancer biomarkers.American journal of cancer research · 2023Article
- Insight into Extracellular Vesicle-Cell Communication: From Cell Recognition to Intracellular Fate.Cells · 2022Review
- Extracellular Vesicles in Pathogenesis and Treatment of Metabolic Associated Fatty Liver Disease.Frontiers in physiology · 2022Review
- The dipeptide prolyl-hydroxyproline promotes cellular homeostasis and lamellipodia-driven motility via active β1-integrin in adult tendon cells.The Journal of biological chemistry · 2021Article
- Mechanism of idiosyncratic drug induced liver injury (DILI): unresolved basic issues.Annals of translational medicine · 2021Review
- Idiosyncratic Drug-Induced Liver Injury: Mechanistic and Clinical Challenges.International journal of molecular sciences · 2021Review
- Recent Advances in Models of Immune-Mediated Drug-Induced Liver Injury.Frontiers in toxicology · 2021Review
- Extracellular vesicles: Roles and applications in drug-induced liver injury.Advances in clinical chemistry · 2021Review
- Review
- Clinical applications of exosome membrane proteins.Precision clinical medicine · 2020Review
- Hijacking Endocytosis and Autophagy in Extracellular Vesicle Communication: Where the Inside Meets the Outside.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Idiosyncratic drug-induced liver injury (DILI) is a rare, often difficult-to-predict adverse reaction with complex pathomechanisms. However, it is now evident that certain forms of DILI are immune-mediated and may involve the activation of drug-specific T cells. Exosomes are cell-derived vesicles that carry RNA, lipids, and protein cargo from their cell of origin to distant cells, and they may play a role in immune activation. Herein, primary human hepatocytes were treated with drugs associated with a high incidence of DILI (flucloxacillin, amoxicillin, isoniazid, and nitroso-sulfamethoxazole) to characterize the proteins packaged within exosomes that are subsequently transported to dendritic cells for processing. Exosomes measured between 50 and 100 nm and expressed enriched CD63. Liquid chromatography-tandem mass spectrometry (LC/MS-MS) identified 2,109 proteins, with 608 proteins being quantified across all exosome samples. Data are available through ProteomeXchange with identifier PXD010760. Analysis of gene ontologies revealed that exosomes mirrored whole human liver tissue in terms of the families of proteins present, regardless of drug treatment. However, exosomes from nitroso-sulfamethoxazole-treated hepatocytes selectively packaged a specific subset of proteins. LC/MS-MS also revealed the presence of hepatocyte-derived exosomal proteins covalently modified with amoxicillin, flucloxacillin, and nitroso-sulfamethoxazole. Uptake of exosomes by monocyte-derived dendritic cells occurred silently, mainly through phagocytosis, and was inhibited by latrunculin A. An amoxicillin-modified 9-mer peptide derived from the exosomal transcription factor protein SRY (sex determining region Y)-box 30 activated naïve T cells from human leukocyte antigen A*02:01-positive human donors. Conclusion: This study shows that exosomes have the potential to transmit drug-specific hepatocyte-derived signals to the immune system and provide a pathway for the induction of drug hapten-specific T-cell responses.
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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.