Toll-like receptor 2 and facial motoneuron survival after facial nerve axotomy.

Toll-like receptor 2 and facial motoneuron survival after facial nerve axotomy.
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DOI:
10.1016/j.neulet.2009.12.076
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发表时间:
2010-02-26
影响因子:
2.5
通讯作者:
Jones KJ
Jones KJ
中科院分区:
医学4区
文献类型:
--
作者:
Wainwright DA;Xin J;Mesnard NA;Sanders VM;Jones KJ

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我们之前已经证明,CD4+ Th2淋巴细胞通过与外周抗原呈递细胞以及中枢神经系统内小胶质细胞的相互作用,在面神经剪断后拯救面部运动神经元(FMN)的存活是必需的。此外,先天免疫分子toll样受体2 (TLR2)与th2型免疫反应的发展有关,并可被死亡或垂死细胞释放的细胞内成分激活。本研究通过在小鼠茎突突孔处进行面神经轴突切开术,在血脑屏障(BBB)不通透的情况下,探讨了TLR2在FMN对轴突切开术反应中的作用。面神经截轴后,TLR2 mRNA在面神经运动核中显著上调,共免疫荧光将TLR2定位于CD68+小胶质细胞,而不是GFAP+星形胶质细胞。使用TLR2缺陷(TLR2−/−)小鼠,确定TLR2不影响腋切开术后FMN存活水平。这些数据有助于理解FMN死亡后先天免疫的作用,并可能与肌萎缩侧索硬化症(ALS)等运动神经元疾病有关。
We have previously demonstrated that CD4+ Th2 lymphocytes are required to rescue facial motoneuron (FMN) survival after facial nerve axotomy through interaction with peripheral antigen presenting cells, as well as CNS resident microglia. Furthermore, the innate immune molecule, toll-like receptor 2 (TLR2), has been implicated in the development of Th2-type immune responses and can be activated by intracellular components released by dead or dying cells. The role of TLR2 in the FMN response to axotomy was explored in this study, using a model of facial nerve axotomy at the stylomastoid foramen in the mouse, in which blood-brain-barrier (BBB) permeability does not occur. After facial nerve axotomy, TLR2 mRNA was significantly upregulated in the facial motor nucleus and co-immunofluorescence localized TLR2 to CD68+ microglia, but not GFAP+ astrocytes. Using TLR2-deficient (TLR2−/−) mice, it was determined that TLR2 does not affect FMN survival levels after axotomy. These data contribute to understanding the role of innate immunity after FMN death and may be relevant to motoneuron diseases, such as amyotrophic lateral sclerosis (ALS).
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