PXD026998-1

PXD026998 is an original dataset announced via ProteomeXchange.

Title	Pro-inflammatory Beta Cell Small Extracellular Vesicles Induce Beta Cell Failure Through Activation of the CXCL10/CXCR3 Axis in Diabetes
Description	Coordinated communication among pancreatic islet cells is necessary for the maintenance of glucose homeostasis. In diabetes, chronic exposure to pro-inflammatory cytokines has been shown to perturb β-cell communication and function. Compelling evidence has implicated extracellular vesicles (EVs) in modulating physiological and pathological responses to β-cell stress. We report that pro-inflammatory β-cell small EVs (cytoEV) induce β-cell dysfunction, promote a pro-inflammatory islet transcriptome, and enhance recruitment of CD8+ T-cells and macrophages. Proteomic analysis of cytoEV revealed an enrichment of the chemokine, CXCL10, with surface topological analysis depicting CXCL10 as membrane-bound on cytoEV to facilitate direct binding to CXCR3 receptors on the surface of β-cells. CXCR3 receptor inhibition reduced CXCL10-cytoEV binding and attenuated β-cell dysfunction, inflammatory gene expression, and leukocyte recruitment to islets. Collectively, this work implicates the significant role of pro-inflammatory β-cell derived small EVs in modulating β-cell function, global gene expression, and antigen presentation through activation of the CXCL10/CXCR3 axis.
HostingRepository	PRIDE
AnnounceDate	2021-08-25
AnnouncementXML	Submission_2021-08-25_05:47:12.488.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Naureen Javeed
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-29 21:15:52	ID requested
⏵ 1	2021-08-25 05:47:12	announced

Dataset with its publication pending

submitter keyword: Extracellular vesicles, β-cell, inflammation, diabetes, intercellular communication, CXCL10

Naureen Javeed
contact affiliation	Mayo Clinic Department of Physiology and Biomedical Engineering Rochester, MN 55901
contact email	javeed.naureen@mayo.edu
lab head
Naureen Javeed
contact affiliation	Mayo Clinic
contact email	javeed.naureen@mayo.edu
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/2021/08/PXD026998

PRIDE project URI

• PRIDE
  1. PXD026998
     1. Label: PRIDE project
     2. Name: Pro-inflammatory Beta Cell Small Extracellular Vesicles Induce Beta Cell Failure Through Activation of the CXCL10/CXCR3 Axis in Diabetes