Identification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus‐derived extracellular vesicles
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. Interestin...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2016-09-01
|
| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201606271 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849343779634413568 |
|---|---|
| author | Sriram Balusu Elien Van Wonterghem Riet De Rycke Koen Raemdonck Stephan Stremersch Kris Gevaert Marjana Brkic Delphine Demeestere Valerie Vanhooren An Hendrix Claude Libert Roosmarijn E Vandenbroucke |
| author_facet | Sriram Balusu Elien Van Wonterghem Riet De Rycke Koen Raemdonck Stephan Stremersch Kris Gevaert Marjana Brkic Delphine Demeestere Valerie Vanhooren An Hendrix Claude Libert Roosmarijn E Vandenbroucke |
| author_sort | Sriram Balusu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6d64e554a98c44b7a2568b682bcc28e6 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2016-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-6d64e554a98c44b7a2568b682bcc28e62025-08-20T03:42:52ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842016-09-018101162118310.15252/emmm.201606271Identification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus‐derived extracellular vesiclesSriram Balusu0Elien Van Wonterghem1Riet De Rycke2Koen Raemdonck3Stephan Stremersch4Kris Gevaert5Marjana Brkic6Delphine Demeestere7Valerie Vanhooren8An Hendrix9Claude Libert10Roosmarijn E Vandenbroucke11Inflammation Research Center, VIBInflammation Research Center, VIBInflammation Research Center, VIBLaboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent UniversityLaboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent UniversityDepartment of Medical Protein Research, VIBInflammation Research Center, VIBInflammation Research Center, VIBInflammation Research Center, VIBLaboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent UniversityInflammation Research Center, VIBInflammation Research Center, VIBAbstract 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.https://doi.org/10.15252/emmm.201606271blood–brain barrierchoroid plexusexosomesextracellular vesiclessepsis |
| spellingShingle | Sriram Balusu Elien Van Wonterghem Riet De Rycke Koen Raemdonck Stephan Stremersch Kris Gevaert Marjana Brkic Delphine Demeestere Valerie Vanhooren An Hendrix Claude Libert Roosmarijn E Vandenbroucke Identification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus‐derived extracellular vesicles EMBO Molecular Medicine blood–brain barrier choroid plexus exosomes extracellular vesicles sepsis |
| title | Identification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus‐derived extracellular vesicles |
| title_full | Identification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus‐derived extracellular vesicles |
| title_fullStr | Identification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus‐derived extracellular vesicles |
| title_full_unstemmed | Identification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus‐derived extracellular vesicles |
| title_short | Identification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus‐derived extracellular vesicles |
| title_sort | identification of a novel mechanism of blood brain communication during peripheral inflammation via choroid plexus derived extracellular vesicles |
| topic | blood–brain barrier choroid plexus exosomes extracellular vesicles sepsis |
| url | https://doi.org/10.15252/emmm.201606271 |
| work_keys_str_mv | AT srirambalusu identificationofanovelmechanismofbloodbraincommunicationduringperipheralinflammationviachoroidplexusderivedextracellularvesicles AT elienvanwonterghem identificationofanovelmechanismofbloodbraincommunicationduringperipheralinflammationviachoroidplexusderivedextracellularvesicles AT rietderycke identificationofanovelmechanismofbloodbraincommunicationduringperipheralinflammationviachoroidplexusderivedextracellularvesicles AT koenraemdonck identificationofanovelmechanismofbloodbraincommunicationduringperipheralinflammationviachoroidplexusderivedextracellularvesicles AT stephanstremersch identificationofanovelmechanismofbloodbraincommunicationduringperipheralinflammationviachoroidplexusderivedextracellularvesicles AT krisgevaert identificationofanovelmechanismofbloodbraincommunicationduringperipheralinflammationviachoroidplexusderivedextracellularvesicles AT marjanabrkic identificationofanovelmechanismofbloodbraincommunicationduringperipheralinflammationviachoroidplexusderivedextracellularvesicles AT delphinedemeestere identificationofanovelmechanismofbloodbraincommunicationduringperipheralinflammationviachoroidplexusderivedextracellularvesicles AT valerievanhooren identificationofanovelmechanismofbloodbraincommunicationduringperipheralinflammationviachoroidplexusderivedextracellularvesicles AT anhendrix identificationofanovelmechanismofbloodbraincommunicationduringperipheralinflammationviachoroidplexusderivedextracellularvesicles AT claudelibert identificationofanovelmechanismofbloodbraincommunicationduringperipheralinflammationviachoroidplexusderivedextracellularvesicles AT roosmarijnevandenbroucke identificationofanovelmechanismofbloodbraincommunicationduringperipheralinflammationviachoroidplexusderivedextracellularvesicles |