PXD062615

PXD062615 is an original dataset announced via ProteomeXchange.

Title	Temporal changes in the protein cargo of extracellular vesicles and resultant immune reprogramming after severe burn injury in humans and mice.
Description	Introduction Severe injury, including burn trauma, leads to profound immune dysfunction, yet the mechanisms driving these changes remain incompletely defined. This lack of understanding has hindered efforts to modulate the immune response effectively. Additionally, a clear biomarker profile to guide clinicians in identifying burn patients at high risk for poor clinical outcomes is lacking. Extracellular vesicles (EVs) have emerged as novel mediators of immune dysfunction in various pathologies. Prior studies in mouse models have demonstrated that plasma EVs increase following burn injury and contribute to immune dysfunction. Furthermore, EVs have potential as biomarkers for predicting extended hospital stays in burn patients. This study hypothesizes that human EVs, purified early and late after burn injury, will exhibit immune reprogramming effects similar to those observed in mice and that specific EV protein cargo may serve as biomarkers of immune and physiological responses to burn injury. Methods EVs were isolated from the plasma of burn-injury patients at early (<72h) and late (≥14 days) time points post-injury. Using unbiased immune transcriptome and bioinformatic causal network analyses, the immunomodulatory effects of these EVs were assessed in human THP-1 macrophages. Mass spectrometry-based quantitative proteomics and pathway analyses were conducted to characterize the protein cargo of EVs from both human and mouse models at different post-burn phases. Results Early post-burn human EVs induced significant immune reprogramming in macrophages, increasing pro-inflammatory signaling while suppressing anti-inflammatory pathways. In contrast, late post-burn EVs exhibited an immunosuppressive profile, with downregulation of pro-inflammatory pathways and upregulation of anti-inflammatory signaling. Proteomic analyses revealed that human and mouse EVs contained unique and overlapping protein cargo across different time points. At day 7 post-burn, mouse EVs were enriched in circulation/complement and neuronal proteins, whereas by day 14, reductions in membrane and metabolism-associated proteins were observed. Similarly, in human EVs at 14 days post-burn, increased levels of circulation/complement, immune, and transport proteins were detected. Conclusions EVs from burn-injury patients at distinct time points differentially modulate immune responses in macrophages, mirroring the temporal immune phenotypes observed in clinical settings. These findings suggest that EV-macrophage interactions play a crucial role in burn-induced immune dysfunction and highlight the potential of EV protein cargo as biomarkers for immune status and patient outcomes following burn injury.
HostingRepository	PRIDE
AnnounceDate	2025-05-21
AnnouncementXML	Submission_2025-05-21_06:45:41.699.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Angie Mordant
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-04 08:47:10	ID requested
⏵ 1	2025-05-21 06:45:42	announced

Dataset with its publication pending

submitter keyword: protein cargo, extracellular vesicles, macrophages, burn injury, thermal injury,Burn injury

Robert Maile
contact affiliation	Department of Surgery, University of Florida, Gainesville, FL, USA; Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida, Gainesville, FL, USA
contact email	Robert.maile@surgry.ufl.edu
lab head
Angie Mordant
contact affiliation	UNC Proteomics Core, Department of Pharmacology, University of North Carolina at Chapel Hill
contact email	angie_mordant@med.unc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062615
     1. Label: PRIDE project
     2. Name: Temporal changes in the protein cargo of extracellular vesicles and resultant immune reprogramming after severe burn injury in humans and mice.