PXD010760

PXD010760 is an original dataset announced via ProteomeXchange.

Title	Exosomal transport of hepatocyte-derived drug-modified proteins to the immune system
Description	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 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 50-100 nm and expressed CD63. LC-MS/MS identified an average of 1200 proteins across all exosome samples. 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 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 mainly via phagocytosis, and was inhibited by latrunculin A. This study reveals that exosomes have the potential to transmit drug-specific hepatocyte-derived signals to the immune system and provides a pathway for the induction of drug hapten-specific T-cell responses.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:47:38.896.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rosalind Jenkins
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; deamidated residue
Instrument	SCIEX instrument model

Revision	Datetime	Status	ChangeLog Entry
0	2018-08-13 07:38:50	ID requested
1	2019-05-14 07:16:12	announced
⏵ 2	2024-10-22 04:47:41	announced	2024-10-22: Updated project metadata.

Ogese MO, Jenkins RE, Adair K, Tailor A, Meng X, Faulkner L, Enyindah BO, Schofield A, Diaz-Nieto R, Ressel L, Eagle GL, Kitteringham NR, Goldring CE, Park BK, Naisbitt DJ, Betts C, Exosomal Transport of Hepatocyte-Derived Drug-Modified Proteins to the Immune System. Hepatology, 70(5):1732-1749(2019) [pubmed]

10.1002/hep.30701;

curator keyword: Biological, Biomedical

submitter keyword: exosomes,Hepatocytes, immune response, drug-induced liver injury

Rosalind Jenkins
contact affiliation	MRC Centre for Drug Safety Science, Dept Molecular and Clinical Pharmacology, University of Liverpool
contact email	R.Jenkins@liv.ac.uk
lab head
Rosalind Jenkins
contact affiliation	University of Liverpool
contact email	R.Jenkins@liv.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD010760

PRIDE project URI

• PRIDE
  1. PXD010760
     1. Label: PRIDE project
     2. Name: Exosomal transport of hepatocyte-derived drug-modified proteins to the immune system