PXD006087

PXD006087 is an original dataset announced via ProteomeXchange.

Title	Astrocyte-shed extracellular vesicles regulate the peripheral leukocyte response to inflammatory brain lesions
Description	Brain injury induces a peripheral acute cytokine response (ACR) that directs the transmigration of leukocytes into brain. This brain-to-peripheral immune communication affects patient recovery, thus understanding how it is regulated is important. Contrary to expectations it is not regulated by sympathetic innervation. Using a mouse model of an inflammatory brain injuryXXX , we set out to find a soluble mediator for this phenomenon. We found that extracellular vesicles (EVs) shed from astrocytes in response to intracerbral injection of interleukin-1 (IL-1) rapidly entered into peripheral circulation and promoted the transmigration of leukocytes through modulation of the peripheral ACR. Bioinformatic interrogation of the protein and miRNA cargo of EVs identified Peroxisome proliferator-activated receptor-α (PPAR-α) as a primary molecular target of astrocyte-shed EVs. We confirmed in mice that astrocytic EVs promoted the transmigration of leukocytes into the brain by modulating inhibiting PPAR and presumably subsequentlyresulting in the increase of NF-κB activity thus, triggering the production of cytokines in liver. These findings expand our basic understanding of the mechanisms regulating communication between the brain and peripheral immune system, and identify astrocytic EVs as a molecular regulator of the immunological response to inflammatory brain damage.
HostingRepository	PRIDE
AnnounceDate	2018-10-26
AnnouncementXML	Submission_2018-10-26_09:09:27.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex Dickens
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2017-03-14 02:46:15	ID requested
⏵ 1	2018-10-26 09:09:28	announced

Dickens AM, Tovar-Y-Romo LB, Yoo SW, Trout AL, Bae M, Kanmogne M, Megra B, Williams DW, Witwer KW, Gacias M, Tabatadze N, Cole RN, Casaccia P, Berman JW, Anthony DC, Haughey NJ, Astrocyte-shed extracellular vesicles regulate the peripheral leukocyte response to inflammatory brain lesions. Sci Signal, 10(473):(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: Extracellular vesicles, IL-1beta, brain injury, neuroinflammation

Norman J Haughey
contact affiliation	Departments of Neurology and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA, 21287;
contact email	nhauge1@jhmi.edu
lab head
Alex Dickens
contact affiliation	University of Turku
contact email	alex.dickens@utu.fi
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/2018/10/PXD006087

PRIDE project URI

• PRIDE
  1. PXD006087
     1. Label: PRIDE project
     2. Name: Astrocyte-shed extracellular vesicles regulate the peripheral leukocyte response to inflammatory brain lesions