Vagus Nerve Stimulation Regulates the Th17/Treg Balance and Alleviates Lung Injury in Acute Respiratory Distress Syndrome by Upregulating α7nAChR
<b>Background:</b> Acute respiratory distress syndrome (ARDS) is a high-mortality disease strongly associated with an imbalance in the inflammatory response. The ratio of helper T 17 (Th17) cells to regulatory T (Treg) cells is significantly correlated with prognosis and outcomes in ARDS...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
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| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/6/1294 |
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| Summary: | <b>Background:</b> Acute respiratory distress syndrome (ARDS) is a high-mortality disease strongly associated with an imbalance in the inflammatory response. The ratio of helper T 17 (Th17) cells to regulatory T (Treg) cells is significantly correlated with prognosis and outcomes in ARDS. Vagus nerve stimulation (VNS) alleviates lung injury in ARDS model rats. The objective of this study was to further investigate whether VNS attenuates lipopolysaccharide-induced ARDS by regulating Th17/Treg homeostasis and to explore the underlying mechanisms. <b>Methods</b>: We assessed the degree of lung injury using hematoxylin and eosin staining, the lung wet-to-dry ratio, and total protein and pro-inflammatory cytokine levels in bronchoalveolar lavage fluid. The expression levels of Th17 and Treg cells were determined using flow cytometry, Western blotting, quantitative real-time PCR, and enzyme-linked immunosorbent assays. <b>Results</b>: We found that VNS reduced lung injury in ARDS model rats. Additionally, VNS regulated Th17/Treg homeostasis and reduced the levels of inflammatory factors in both the lungs and spleens. Notably, the effects of VNS were consistent when the afferent or efferent vagus nerve, or both, were stimulated. Further investigation revealed that VNS upregulated splenic α7 nicotinic acetylcholine receptors (α7nAChRs). The administration of an α7nAChR agonist enhanced VNS-mediated regulation of Th17/Treg homeostasis and attenuated lung injury, while these effects were blocked by α7nAChR antagonists. <b>Conclusions</b>: Our study demonstrated that VNS regulates the Th17/Treg balance through α7nAChR activation in the spleen, thereby mitigating lung injury in ARDS. These findings provide new theoretical support for the use of VNS in attenuating ARDS. |
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| ISSN: | 2227-9059 |