肝是重要的免疫器官，肝炎是非酒精性脂肪性肝病病理生理的一部分，这种情况可能会促进肝硬化、肝癌、肝衰竭和心血管疾病的发生。虽然肝脏实质神经密集，但我们很少了解肝脏功能在炎症中的神经调节。在这里，我们研究迷走神经对急性炎症下肝脏响应的控制。雄性C57BL/6J小鼠接受假手术、手术迷走神经或电刺激迷走神经，然后经腹腔注射TLR2激动剂酵母壁多糖。动物在注射后12小时安乐死并收集组织。样本通过qPCR、RNAseq、流式细胞术或ELISA分析。在接受迷走神经切断手术的小鼠中，肝脏炎症介质Ccl2、Il-1β和Tnf-α的mRNA水平明显高于接受假手术的小鼠。治疗组之间Ccl2水平的差异在大多数情况下都反映在血浆趋化因子CCL2的浓度上。相应地，我们观察到流式细胞术测得的腹腔巨噬细胞数量在接受迷走神经切断手术的小鼠中比接受假手术的小鼠要高。在接受电刺激迷走神经的小鼠中，Ccl2、Il1β和Tnf-α的肝脏mRNA水平以及血浆CCL2水平明显低于接受假手术的小鼠。有趣的是，RNAseq显示了肝星状细胞（HSC）的重要活化标记物Pnpla3是迷走神经切断组和假手术组之间最显着的差异表达基因。值得注意的是，脂肪肝引起的多个HSC激活相关转录本在迷走神经切断组中更高，这表明迷走神经信号有助于HSC激活。支持这一点的是，我们观察到流式细胞术测得的激活HSC数量在接受迷走神经切断手术的小鼠中比接受假手术的小鼠要高。颈部迷走神经信号控制了酵母壁多糖诱导的腹膜炎下肝脏炎症和HSC活化标志物。© 2023. 作者。

The liver is an important immunological organ and liver inflammation is part of the pathophysiology of non-alcoholic steatohepatitis, a condition that may promote cirrhosis, liver cancer, liver failure, and cardiovascular disease. Despite dense innervation of the liver parenchyma, little is known about neural regulation of liver function in inflammation. Here, we study vagus nerve control of the liver response to acute inflammation.Male C57BL/6 J mice were subjected to either sham surgery, surgical vagotomy, or electrical vagus nerve stimulation followed by intraperitoneal injection of the TLR2 agonist zymosan. Animals were euthanized and tissues collected 12 h after injection. Samples were analyzed by qPCR, RNAseq, flow cytometry, or ELISA.Hepatic mRNA levels of pro-inflammatory mediators Ccl2, Il-1β, and Tnf-α were significantly higher in vagotomized mice compared with mice subjected to sham surgery. Differences in liver Ccl2 levels between treatment groups were largely reflected in the plasma chemokine (C-C motif) ligand 2 (CCL2) concentration. In line with this, we observed a higher number of macrophages in the livers of vagotomized mice compared with sham as measured by flow cytometry. In mice subjected to electrical vagus nerve stimulation, hepatic mRNA levels of Ccl2, Il1β, and Tnf-α, and plasma CCL2 levels, were significantly lower compared with sham. Interestingly, RNAseq revealed that a key activation marker for hepatic stellate cells (HSC), Pnpla3, was the most significantly differentially expressed gene between vagotomized and sham mice. Of note, several HSC-activation associated transcripts were higher in vagotomized mice, suggesting that signals in the vagus nerve contribute to HSC activation. In support of this, we observed significantly higher number of activated HSCs in vagotomized mice as compared with sham as measured by flow cytometry.Signals in the cervical vagus nerve controlled hepatic inflammation and markers of HSC activation in zymosan-induced peritonitis.© 2023. The Author(s).