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

被引：277

作者：

Balusu, Sriram ^{[1
,2
,3
,4
]}

Van Wonterghem, Ellen ^{[1
,2
]}

De Rycke, Riet ^{[1
,2
]}

Raemdonck, Koen ^{[5
]}

Stremersch, Stephan ^{[5
]}

Gevaert, Kris ^{[3
,4
]}

Brkic, Marjana ^{[1
,2
,6
]}

Demeestere, Delphine ^{[1
,2
]}

Vanhooren, Valerie ^{[1
,2
]}

Hendrix, An ^{[7
]}

Libert, Claude ^{[1
,2
]}

Vandenbroucke, Roosmarijn E. ^{[1
,2
]}

机构：

[1] VIB, Inflammat Res Ctr, Ghent, Belgium

[2] Univ Ghent, Dept Biomed Mol Biol, Ghent, Belgium

[3] VIB, Dept Med Prot Res, Ghent, Belgium

[4] Univ Ghent, Dept Biochem, Ghent, Belgium

[5] Univ Ghent, Fac Pharmaceut Sci, Lab Gen Biochem & Phys Pharm, Ghent, Belgium

[6] Univ Belgrade, Inst Biol Res, Dept Neurobiol, Belgrade, Serbia

[7] Univ Ghent, Dept Radiat Oncol & Expt Canc Res, Lab Expt Canc Res, Ghent, Belgium

来源：

EMBO MOLECULAR MEDICINE | 2016年 / 8卷 / 10期

关键词：

blood-brain barrier; choroid plexus; exosomes; extracellular vesicles; sepsis; CEREBROSPINAL FLUID INTERFACE; DENDRITIC CELLS; NERVOUS-SYSTEM; EMERGING ROLES; CSF BARRIER; INTERCELLULAR COMMUNICATION; NEURODEGENERATIVE DISEASES; ALZHEIMERS-DISEASE; PROTEOMIC ANALYSIS; IMMUNE-RESPONSE;

D O I：

10.15252/emmm.201606271

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：1162 / 1183

页数：22

共 81 条

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