Dcf1 Deficiency Attenuates the Role of Activated Microglia During Neuroinflammation.
Dcf1 Deficiency Attenuates the Role of Activated Microglia During Neuroinflammation.
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DCf1 缺乏会减弱激活的小胶质细胞在神经炎症过程中的作用
DOI：
10.3389/fnmol.2018.00256
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发表时间：
2018
影响因子：
4.8
通讯作者：
Wen T
中科院分区：
文献类型：
--
作者：
Wang J;Li J;Wang Q;Kong Y;Zhou F;Li Q;Li W;Sun Y;Wang Y;Guan Y;Wu M;Wen T
小胶质细胞作为主要的免疫细胞，在中枢神经系统中起着至关重要的作用，通过迁移和执行吞噬作用对神经炎症作出反应。树突状细胞衍生因子1（Dcf 1）在神经干细胞分化、胶质瘤凋亡、树突棘形成和阿尔茨海默病（AD）中起重要作用，但Dcf 1基因参与脑免疫应答的研究尚未见报道。本研究通过对Dcf 1-/-（Dcf 1-KO）小鼠的RNA测序和功能富集分析，发现Dcf 1-/-（Dcf 1-KO）小鼠中下调的基因主要与免疫相关。体内实验表明，Dcf 1缺失对小胶质细胞功能产生了深远的影响，增加了小胶质细胞活化标志物的表达，如离子钙结合衔接分子1（Iba 1）、分化簇68（CD 68）和转运蛋白（TSPO），以及某些促炎细胞因子（Cxcl 1、Ccl 7和IL 17 D），但降低了小胶质细胞的迁移和吞噬能力，并降低了小鼠海马中一些其他促炎细胞因子（考克斯-2、IL-1β、IL-6、TNF-α和Csf 1）的表达水平。此外，体外实验显示，在不存在脂多糖（LPS）的情况下，大多数小胶质细胞被分化并以静息状态存在，仅约10%的细胞表现出变形虫样形态，指示活化状态。LPS处理显著增加了活化细胞与静息细胞的比例，Dcf 1下调进一步增加了这一比例。这些数据表明，Dcf 1缺失介导神经炎症，并诱导激活的小胶质细胞功能障碍，阻止迁移和吞噬作用的执行。这些发现支持进一步研究小胶质细胞相关神经炎性疾病的生物学机制，以及Dcf 1在免疫应答中的作用。
Microglia serve as the principal immune cells and play crucial roles in the central nervous system, responding to neuroinflammation via migration and the execution of phagocytosis. Dendritic cell-derived factor 1 (Dcf1) is known to play an important role in neural stem cell differentiation, glioma apoptosis, dendritic spine formation, and Alzheimer’s disease (AD), nevertheless, the involvement of the Dcf1 gene in the brain immune response has not yet been reported. In the present paper, the RNA-sequencing and function enrichment analysis suggested that the majority of the down-regulated genes in Dcf1-/- (Dcf1-KO) mice are immune-related. In vivo experiments showed that Dcf1 deletion produced profound effects on microglial function, increased the expression of microglial activation markers, such as ionized calcium binding adaptor molecule 1 (Iba1), Cluster of Differentiation 68 (CD68) and translocator protein (TSPO), as well as certain proinflammatory cytokines (Cxcl1, Ccl7, and IL17D), but decreased the migratory and phagocytic abilities of microglial cells, and reduced the expression levels of some other proinflammatory cytokines (Cox-2, IL-1β, IL-6, TNF-α, and Csf1) in the mouse hippocampus. Furthermore, in vitro experiments revealed that in the absence of lipopolysaccharide (LPS), the majority of microglia were ramified and existed in a resting state, with only approximately 10% of cells exhibiting an amoeboid-like morphology, indicative of an activated state. LPS treatment dramatically increased the ratio of activated to resting cells, and Dcf1 downregulation further increased this ratio. These data indicated that Dcf1 deletion mediates neuroinflammation and induces dysfunction of activated microglia, preventing migration and the execution of phagocytosis. These findings support further investigation into the biological mechanisms underlying microglia-related neuroinflammatory diseases, and the role of Dcf1 in the immune response.
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影响因子：
4.7
作者：
Andreasson KI;Bachstetter AD;Colonna M;Ginhoux F;Holmes C;Lamb B;Landreth G;Lee DC;Low D;Lynch MA;Monsonego A;O'Banion MK;Pekny M;Puschmann T;Russek-Blum N;Sandusky LA;Selenica ML;Takata K;Teeling J;Town T;Van Eldik LJ
通讯作者：
Van Eldik LJ
影响因子：
5.1
作者：
Fu, Ruying;Shen, Qingyu;Xu, Pengfei;Luo, Jin Jun;Tang, Yamei
通讯作者：
Tang, Yamei
影响因子：
3.3
作者：
Felger JC;Lotrich FE
通讯作者：
Lotrich FE
影响因子：
9.2
作者：
Erta M;Quintana A;Hidalgo J
通讯作者：
Hidalgo J
影响因子：
6.2
作者：
Imai, Y;Kohsaka, S
通讯作者：
Kohsaka, S