Open AccessIdentification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus‐derived extracellular vesicles
Author(s) -
Balusu Sriram,
Van Wonterghem Elien,
De Rycke Riet,
Raemdonck Koen,
Stremersch Stephan,
Gevaert Kris,
Brkic Marjana,
Demeestere Delphine,
Vanhooren Valerie,
Hendrix An,
Libert Claude,
Vandenbroucke Roosmarijn E
Publication year - 2016
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201606271
Subject(s) - choroid plexus , inflammation , microvesicles , extracellular vesicles , microbiology and biotechnology , mechanism (biology) , extracellular , peripheral blood , identification (biology) , cerebrospinal fluid , vesicle , blood–brain barrier , pathology , chemistry , medicine , neuroscience , biology , immunology , central nervous system , microrna , biochemistry , gene , philosophy , botany , epistemology , membrane
Here, we identified release of extracellular vesicles (EVs) by the choroid plexus epithelium ( CPE ) as a new mechanism of blood–brain communication. Systemic inflammation induced an increase in EVs and associated pro‐inflammatory mi RNA s, including miR‐146a and miR‐155, in the CSF . Interestingly, this was associated with an increase in amount of multivesicular bodies ( MVB s) and exosomes per MVB in the CPE cells. Additionally, we could mimic this using LPS ‐stimulated primary CPE cells and choroid plexus explants. These choroid plexus‐derived EVs can enter the brain parenchyma and are taken up by astrocytes and microglia, inducing mi RNA target repression and inflammatory gene up‐regulation. Interestingly, this could be blocked in vivo by intracerebroventricular (icv) injection of an inhibitor of exosome production. Our data show that CPE cells sense and transmit information about the peripheral inflammatory status to the central nervous system ( CNS ) via the release of EVs into the CSF , which transfer this pro‐inflammatory message to recipient brain cells. Additionally, we revealed that blockage of EV secretion decreases brain inflammation, which opens up new avenues to treat systemic inflammatory diseases such as sepsis.