School of Medicine, Texas A&M University, 8447 Riverside Parkway, Bryan, TX 77807, USA.
BCell Solutions, Inc., Colorado Springs, CO 80907, USA.
Int J Mol Sci. 2022 Aug 30;23(17):9851. doi: 10.3390/ijms23179851.
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 CD11b and CD11b 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.
TBI 诱导脾脏 B 和 T 细胞扩增，导致神经炎症和神经退行性变。迷走神经是颅神经中最长的一条，是主要的副交感神经通路，允许中枢神经系统 (CNS) 控制外周器官，包括调节炎症反应。实现这一目标的一种方法是通过迷走神经支配腹腔神经节，从中脾神经支配脾脏。这种脾脏神经支配使脾脏免疫反应的调节成为可能，包括脾细胞的选择、激活和下游信号转导。考虑到左右迷走神经有不同的路径，它们可能会在中枢神经系统损伤后对脾脏免疫反应产生不同的影响。为了验证这一可能性，我们对免疫细胞亚群进行了分析和定量，分别进行了左侧或右侧单侧迷走神经切断术。双侧单侧迷走神经切断术在 B 细胞百分比以及迷走神经切断术后巨噬细胞和 T 细胞百分比下降方面都产生了相似的影响。接下来，我们测试了左侧单侧迷走神经切断术是否会调节创伤性脑损伤 (TBI) 后的脾脏免疫反应的假说。小鼠在接受流体冲击伤 (FPI) 之前 3 天接受左侧颈迷走神经切断术或假手术，FPI 是一种经过充分验证的小鼠 TBI 模型，可始终引发免疫和神经免疫反应。流式细胞术分析显示，FPI 前迷走神经切断术导致 CLIP+B 细胞和 CD4+、CD25+和 CD8+T 细胞减少。FPI 后迷走神经切断术也导致 CD11b 和 CD11b 巨噬细胞的分布发生改变。因此，通过迷走神经从中枢神经系统向外周传递免疫信号可以作为调节 TBI 后免疫反应的靶点。
