Abstract
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.
Authors
Jing Lu, Keren Chen, Zhihong Cen, Yanlan Huang, Yong Li, LiLi Chen, Weifeng Wu
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