Author:
Liu Tianshu,Fu Yanan,Shi Jiawei,He Shukun,Chen Dandan,Li Wenqu,Chen Yihan,Zhang Li,Lv Qing,Yang Yali,Jin Qiaofeng,Wang Jing,Xie Mingxing
Abstract
Abstract
Background
The cholinergic anti-inflammatory pathway (CAP) has been widely studied to modulate the immune response. Current stimulating strategies are invasive or imprecise. Noninvasive low-intensity pulsed ultrasound (LIPUS) has become increasingly appreciated for targeted neuronal modulation. However, its mechanisms and physiological role on myocarditis remain poorly defined.
Methods
The mouse model of experimental autoimmune myocarditis was established. Low-intensity pulsed ultrasound was targeted at the spleen to stimulate the spleen nerve. Under different ultrasound parameters, histological tests and molecular biology were performed to observe inflammatory lesions and changes in immune cell subsets in the spleen and heart. In addition, we evaluated the dependence of the spleen nerve and cholinergic anti-inflammatory pathway of low-intensity pulsed ultrasound in treating autoimmune myocarditis in mice through different control groups.
Results
The echocardiography and flow cytometry of splenic or heart infiltrating immune cells revealed that splenic ultrasound could alleviate the immune response, regulate the proportion and function of CD4+ Treg and macrophages by activating cholinergic anti-inflammatory pathway, and finally reduce heart inflammatory injury and improve cardiac remodeling, which is as effective as an acetylcholine receptor agonists GTS-21. Transcriptome sequencing showed significant differential expressed genes due to ultrasound modulation.
Conclusions
It is worth noting that the ultrasound therapeutic efficacy depends greatly on acoustic pressure and exposure duration, and the effective targeting organ was the spleen but not the heart. This study provides novel insight into the therapeutic potentials of LIPUS, which are essential for its future application.
Graphical Abstract
Funder
National Natural Science Foundation of China
Key Research and Development Program of Hubei
Shenzhen Science and Technology
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Neurology,Immunology,General Neuroscience
Cited by
1 articles.
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