Unilateral Cervical Vagotomy Modulates Immune Cell Profiles and the Response to a Traumatic Brain Injury.

Unilateral Cervical Vagotomy Modulates Immune Cell Profiles and the Response to a Traumatic Brain Injury.
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DOI:
10.3390/ijms23179851
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发表时间:
2022-08-30
影响因子:
5.6
通讯作者:
Shapiro LA
Shapiro LA
中科院分区:
生物学2区
文献类型:
--
作者:
Newell-Rogers MK;Duong A;Nazarali R;Tobin RP;Rogers SK;Shapiro LA

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脑外伤可导致脾B细胞和T细胞的扩张,从而导致神经炎症和神经变性。迷走神经是最长的脑神经,是中枢神经系统(CNS)控制周围器官的主要副交感神经通路,包括调节炎症反应。其中一种方法是通过迷走神经支配腹腔神经节,脾神经通过迷走神经支配脾。这种脾神经支配能够调节脾的免疫反应,包括脾细胞的选择、激活和下游信号。考虑到左侧和右侧迷走神经的走行不同,它们可能对中枢神经系统损伤后的脾免疫反应产生不同的影响。为了测试这种可能性,在左侧或右侧迷走神经切断术后,对免疫细胞亚群进行了分析和量化。切断一侧迷走神经后,在B细胞百分比、巨噬细胞和T细胞百分比下降方面,两种手术的效果相似。接下来,我们测试了左侧迷走神经切断术将调节脾对创伤性脑损伤(TBI)的免疫反应的假设。小鼠在流体冲击伤(FPI)前3天接受了左侧颈迷走神经切断术或假迷走神经切断术,这是一种具有良好特征的脑损伤小鼠模型,持续引发免疫和神经免疫反应。流式细胞仪分析显示,在FPI之前切断迷走神经导致CLIP+B细胞减少,以及CD4+、CD25+和CD8+T细胞减少。切断迷走神经后的FPI也改变了CD11bHigh和CD11bllow巨噬细胞的分布。因此,通过迷走神经将免疫信号从中枢神经系统传递到外周,可以作为调节脑外伤后免疫反应的靶点。
TBI induces splenic B and T cell expansion that contributes to neuroinflammation and neurodegeneration. The vagus nerve, the longest of the cranial nerves, is the predominant parasympathetic pathway allowing the central nervous system (CNS) control over peripheral organs, including regulation of inflammatory responses. One way this is accomplished is by vagus innervation of the celiac ganglion, from which the splenic nerve innervates the spleen. This splenic innervation enables modulation of the splenic immune response, including splenocyte selection, activation, and downstream signaling. Considering that the left and right vagus nerves have distinct courses, it is possible that they differentially influence the splenic immune response following a CNS injury. To test this possibility, immune cell subsets were profiled and quantified following either a left or a right unilateral vagotomy. Both unilateral vagotomies caused similar effects with respect to the percentage of B cells and in the decreased percentage of macrophages and T cells following vagotomy. We next tested the hypothesis that a left unilateral vagotomy would modulate the splenic immune response to a traumatic brain injury (TBI). Mice received a left cervical vagotomy or a sham vagotomy 3 days prior to a fluid percussion injury (FPI), a well-characterized mouse model of TBI that consistently elicits an immune and neuroimmune response. Flow cytometric analysis showed that vagotomy prior to FPI resulted in fewer CLIP+ B cells, and CD4+, CD25+, and CD8+ T cells. Vagotomy followed by FPI also resulted in an altered distribution of CD11bhigh and CD11blow macrophages. Thus, transduction of immune signals from the CNS to the periphery via the vagus nerve can be targeted to modulate the immune response following TBI.
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