Lu Jing, Chen Keren, Cen Zhihong, Huang Yanlan, Li Yong, Chen LiLi, Wu Weifeng
Department of Cardiology, and.
Emergency Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
JCI Insight. 2025 May 8;10(9). doi: 10.1172/jci.insight.189323.
Patients with viral myocarditis (VMC) exhibit evident autonomic nervous system imbalance, and adverse cardiac remodeling is involved in impaired cholinergic function. The α7 nicotinic acetylcholine receptor (α7nAChR), which is a neurotransmitter receptor, exerts immunoregulatory effects. Recent advances have illuminated the evolution and functions of peripheral and cardiac B cells in heart disease. However, the role of α7nAChR expressed by B cells in the progression of VMC has not been established. We revealed the neuroimmune communication landscape in the heart and found that the phenotypes of cardiac and splenic B cells and their α7nAChR expression changed dynamically during the progression of VMC to dilated cardiomyopathy. α7nAChR on B cells serves as a negative regulator by inhibiting their proinflammatory functions and signaling pathways. B cell-specific α7nAChR deficiency exacerbated myocardial inflammation, fibrosis, and cardiac dysfunction. However, these effects were abrogated in non-B cells from mice with IL-17A knockdown. Enhanced degradation of acetylcholine leads to an imbalance in cholinergic signaling, resulting in impaired neurotransmission. The acetylcholinesterase inhibitor pyridostigmine bromide could improve cardiac remodeling and prevent the progression of VMC to the chronic phase, which was partly dependent on the α7nAChR on B cells. Our findings provide notable insights into cardiac-neural-immune communication during myocardial injury.
病毒性心肌炎（VMC）患者表现出明显的自主神经系统失衡，且不良心脏重塑与胆碱能功能受损有关。α7烟碱型乙酰胆碱受体（α7nAChR）作为一种神经递质受体，具有免疫调节作用。最近的研究进展揭示了外周和心脏B细胞在心脏病中的演变及功能。然而，B细胞表达的α7nAChR在VMC进展中的作用尚未明确。我们揭示了心脏中的神经免疫通讯格局，发现心脏和脾脏B细胞的表型及其α7nAChR表达在VMC向扩张型心肌病进展过程中动态变化。B细胞上的α7nAChR通过抑制其促炎功能和信号通路发挥负调节作用。B细胞特异性α7nAChR缺陷会加剧心肌炎症、纤维化和心脏功能障碍。然而，在白细胞介素-17A基因敲除小鼠的非B细胞中，这些效应被消除。乙酰胆碱降解增强导致胆碱能信号失衡，进而引起神经传递受损。乙酰胆碱酯酶抑制剂溴吡斯的明可改善心脏重塑并防止VMC进展至慢性期，这部分依赖于B细胞上 的α7nAChR。我们的研究结果为心肌损伤期间的心脏-神经-免疫通讯提供了重要见解。
