Neuron-Derived Extracellular Vesicles Modulate Microglia Activation and Function.
Neuron-Derived Extracellular Vesicles Modulate Microglia Activation and Function.
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DOI：
10.3390/biology10100948
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发表时间：
2021-09-22
期刊：
影响因子：
4.2
通讯作者：
Nixon K
中科院分区：
文献类型：
--
作者：
Peng H;Harvey BT;Richards CI;Nixon K
在这项研究中，我们研究了神经元源性细胞外囊泡（NDEV）如何介导原代细胞培养系统中的神经免疫调节。大鼠皮质神经元释放的 EV 可改善小胶质细胞的存活并抑制小胶质细胞上激活标记的表达。此外，NDEV 可减少 LPS 诱导的促炎反应并促进抗炎反应。因此，神经元通过 EV 介导的神经元-胶质细胞通讯来严格调节小胶质细胞活性并控制炎症。小胶质细胞充当中枢神经系统（CNS）的免疫细胞。它们在维持大脑稳态方面发挥着重要作用，而且在调节对损伤的神经免疫反应方面也发挥着重要作用。神经元和小胶质细胞之间的相互作用代表了神经免疫调节及其对中枢神经系统完整性的后续影响的关键过程。然而，神经元-胶质细胞通讯调节小胶质细胞功能的分子机制尚不完全清楚。最近描述的一种细胞间通讯方式是通过纳米大小的细胞外囊泡（EV）在神经元和小胶质细胞之间转移多种分子，例如蛋白质、脂质和核酸。为了确定神经元源性 EV（NDEV）对小胶质细胞的影响，从大鼠皮质神经元的培养上清液中分离出 NDEV。当 NDEV 添加到原代培养的大鼠小胶质细胞中时，我们发现通过抑制细胞凋亡显着提高了小胶质细胞的活力。此外，将NDEV应用于培养的小胶质细胞也抑制了小胶质细胞上活化表面标记的表达。此外，NDEV 通过降低促炎细胞因子（TNF-α、IL-6、MCP-1）和 iNOS 的基因表达来减少 LPS 诱导的小胶质细胞促炎反应，但增加抗炎细胞因子 IL-10 的表达。这些发现支持神经元通过 EV 介导的神经元-胶质细胞通讯严格调节小胶质细胞活动并控制炎症。 （由 R21AA025563 和 R01AA025591 支持）。
In this study we investigated how neuron-derived extracellular vesicles (NDEVs) mediate neuroimmune regulation in primary cell culture systems. Rat cortical neurons released EVs that improved microglial survival and inhibited the expression of activation markers on microglia. Furthermore, NDEVs reduced the LPS-induced proinflammatory response and promoted an anti-inflammatory response. Thus, neurons critically regulate microglia activity and control inflammation via EV-mediated neuron–glia communication. Microglia act as the immune cells of the central nervous system (CNS). They play an important role in maintaining brain homeostasis but also in mediating neuroimmune responses to insult. The interactions between neurons and microglia represent a key process for neuroimmune regulation and subsequent effects on CNS integrity. However, the molecular mechanisms of neuron-glia communication in regulating microglia function are not fully understood. One recently described means of this intercellular communication is via nano-sized extracellular vesicles (EVs) that transfer a large diversity of molecules between neurons and microglia, such as proteins, lipids, and nucleic acids. To determine the effects of neuron-derived EVs (NDEVs) on microglia, NDEVs were isolated from the culture supernatant of rat cortical neurons. When NDEVs were added to primary cultured rat microglia, we found significantly improved microglia viability via inhibition of apoptosis. Additionally, application of NDEVs to cultured microglia also inhibited the expression of activation surface markers on microglia. Furthermore, NDEVs reduced the LPS-induced proinflammatory response in microglia according to reduced gene expression of proinflammatory cytokines (TNF-α, IL-6, MCP-1) and iNOS, but increased expression of the anti-inflammatory cytokine, IL-10. These findings support that neurons critically regulate microglia activity and control inflammation via EV-mediated neuron–glia communication. (Supported by R21AA025563 and R01AA025591).
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影响因子：
3.7
作者：
Lan X;Chen Q;Wang Y;Jia B;Sun L;Zheng J;Peng H
通讯作者：
Peng H
DOI：
10.1073/pnas.0603838103
发表时间：
2006-07-25
影响因子：
11.1
作者：
Rajendran, Lawrence;Honsho, Masanori;Simons, Kai
通讯作者：
Simons, Kai
影响因子：
56.9
作者：
Nimmerjahn, A;Kirchhoff, F;Helmchen, F
通讯作者：
Helmchen, F
影响因子：
--
作者：
Guedes J;Cardoso AL;Pedroso de Lima MC
通讯作者：
Pedroso de Lima MC
DOI：
10.1073/pnas.0308413101
发表时间：
2004-06-29
影响因子：
11.1
作者：
Fevrier, B;Vilette, D;Raposo, G
通讯作者：
Raposo, G