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Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles

Sriram Balusu, Elien Van Wonterghem UGent, Riet De Rycke UGent, Koen Raemdonck UGent, Stephan Stremersch UGent, Kris Gevaert UGent, Marjana Brkić UGent, Delphine Demeestere, Valerie Vanhooren, An Hendrix UGent, et al. (2016) EMBO MOLECULAR MEDICINE. 8(10). p.1162-1183
abstract
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 miRNAs, including miR-146a and miR-155, in the CSF. Interestingly, this was associated with an increase in amount of multivesicular bodies (MVBs) 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 miRNA 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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
ALZHEIMERS-DISEASE, NEURODEGENERATIVE DISEASES, PROTEOMIC ANALYSIS, IMMUNE-RESPONSE, INTERCELLULAR COMMUNICATION, CSF BARRIER, EMERGING ROLES, NERVOUS-SYSTEM, DENDRITIC CELLS, CEREBROSPINAL FLUID INTERFACE, sepsis, extracellular vesicles, exosomes, blood-brain barrier, choroid plexus
journal title
EMBO MOLECULAR MEDICINE
EMBO Mol. Med.
volume
8
issue
10
pages
1162 - 1183
Web of Science type
Article
Web of Science id
000387111700007
ISSN
1757-4684
DOI
10.15252/emmm.201606271
language
English
UGent publication?
yes
classification
A1
additional info
the last two authors contributed equally to this work
copyright statement
I have retained and own the full copyright for this publication
id
8167194
handle
http://hdl.handle.net/1854/LU-8167194
date created
2016-11-24 14:50:23
date last changed
2016-12-19 15:48:24
@article{8167194,
  abstract     = {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 miRNAs, including miR-146a and miR-155, in the CSF. Interestingly, this was associated with an increase in amount of multivesicular bodies (MVBs) 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 miRNA 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.},
  author       = {Balusu, Sriram and Van Wonterghem, Elien and De Rycke, Riet and Raemdonck, Koen and Stremersch, Stephan and Gevaert, Kris and Brki\'{c}, Marjana and Demeestere, Delphine and Vanhooren, Valerie and Hendrix, An and Libert, Claude and Vandenbroucke, Roosmarijn},
  issn         = {1757-4684},
  journal      = {EMBO MOLECULAR MEDICINE},
  keyword      = {ALZHEIMERS-DISEASE,NEURODEGENERATIVE DISEASES,PROTEOMIC ANALYSIS,IMMUNE-RESPONSE,INTERCELLULAR COMMUNICATION,CSF BARRIER,EMERGING ROLES,NERVOUS-SYSTEM,DENDRITIC CELLS,CEREBROSPINAL FLUID INTERFACE,sepsis,extracellular vesicles,exosomes,blood-brain barrier,choroid plexus},
  language     = {eng},
  number       = {10},
  pages        = {1162--1183},
  title        = {Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles},
  url          = {http://dx.doi.org/10.15252/emmm.201606271},
  volume       = {8},
  year         = {2016},
}

Chicago
Balusu, Sriram, Elien Van Wonterghem, Riet De Rycke, Koen Raemdonck, Stephan Stremersch, Kris Gevaert, Marjana Brkic, et al. 2016. “Identification of a Novel Mechanism of Blood-brain Communication During Peripheral Inflammation via Choroid Plexus-derived Extracellular Vesicles.” Embo Molecular Medicine 8 (10): 1162–1183.
APA
Balusu, S., Van Wonterghem, E., De Rycke, R., Raemdonck, K., Stremersch, S., Gevaert, K., Brkic, M., et al. (2016). Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles. EMBO MOLECULAR MEDICINE, 8(10), 1162–1183.
Vancouver
1.
Balusu S, Van Wonterghem E, De Rycke R, Raemdonck K, Stremersch S, Gevaert K, et al. Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles. EMBO MOLECULAR MEDICINE. 2016;8(10):1162–83.
MLA
Balusu, Sriram, Elien Van Wonterghem, Riet De Rycke, et al. “Identification of a Novel Mechanism of Blood-brain Communication During Peripheral Inflammation via Choroid Plexus-derived Extracellular Vesicles.” EMBO MOLECULAR MEDICINE 8.10 (2016): 1162–1183. Print.