Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles.
Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles.
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DOI：
10.15252/emmm.201606271
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发表时间：
2016-10
影响因子：
11.1
通讯作者：
Vandenbroucke RE
中科院分区：
文献类型：
--
作者：
Balusu S;Van Wonterghem E;De Rycke R;Raemdonck K;Stremersch S;Gevaert K;Brkic M;Demeestere D;Vanhooren V;Hendrix A;Libert C;Vandenbroucke RE
在这里，我们确定脉络丛上皮（CPE）的细胞外蔬菜（EV）是血液 - 脑炎症的新机制。 155，在CSF中，这与CPE细胞中每个MVB的多种物体（MVB）和外泌体增加有关使用LPS刺激的原代CPE细胞和脉络丛外植体模仿这些。通过脑室内（ICV）注射外泌体产生的抑制剂的体内被阻断。通过将电动汽车释放到CSF中的中枢神经系统（CNS）的炎症状态，这将这种促炎性信息传递给受体脑细胞，我们透露，EV分泌的阻滞减少了大脑感染治疗脓毒症等全身性炎症性疾病。
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.