Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes
Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes
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DOI：
10.1172/jci83658
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发表时间：
2016-05-01
影响因子：
15.9
通讯作者：
Okusa, Mark D.
中科院分区：
文献类型：
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作者：
Inoue, Tsuyoshi;Abe, Chikara;Okusa, Mark D.
神经系统和免疫系统以复杂的方式相互作用，以维持体内平衡并对压力或损伤做出反应，快速的神经传导可以为调节炎症提供瞬时输入。被称为胆碱能神经通路的炎性反射调节先天性和适应性免疫，并且通过迷走神经刺激（VNS）调节该反射在各种炎性疾病模型中是有效的，例如类风湿性关节炎和炎性肠病。VNS在这些模型中的有效性需要神经信号和脾巨噬细胞上的α 7烟碱乙酰胆碱受体（α 7 nAChR）的整合。在这里，我们试图确定迷走神经的电刺激是否减弱肾脏缺血再灌注损伤（IRI），这促进了促炎分子的释放。在IRI前24小时刺激小鼠迷走神经传入或传出可显著减轻急性肾损伤（阿基）并降低血浆TNF。此外，在VNS和IRI前7天进行脾切除术的动物中，这种保护作用被消除。在缺乏α 7 nAChR的小鼠中，先前的VNS不能预防IRI。相反，过继转移VNS条件α 7 nAChR脾细胞赋予保护受体小鼠IRI。总之，这些结果表明，VNS介导的阿基和全身炎症的减弱取决于α 7 nAChR阳性脾细胞。
The nervous and immune systems interact in complex ways to maintain homeostasis and respond to stress or injury, and rapid nerve conduction can provide instantaneous input for modulating inflammation. The inflammatory reflex referred to as the cholinergic antiinflammatory pathway regulates innate and adaptive immunity, and modulation of this reflex by vagus nerve stimulation (VNS) is effective in various inflammatory disease models, such as rheumatoid arthritis and inflammatory bowel disease. Effectiveness of VNS in these models necessitates the integration of neural signals and alpha 7 nicotinic acetylcholine receptors (alpha 7nAChRs) on splenic macrophages. Here, we sought to determine whether electrical stimulation of the vagus nerve attenuates kidney ischemia-reperfusion injury (IRI), which promotes the release of proinflammatory molecules. Stimulation of vagal afferents or efferents in mice 24 hours before IRI markedly attenuated acute kidney injury (AKI) and decreased plasma TNF. Furthermore, this protection was abolished in animals in which splenectomy was performed 7 days before VNS and IRI. In mice lacking alpha 7nAChR, prior VNS did not prevent IRI. Conversely, adoptive transfer of VNS-conditioned alpha 7nAChR splenocytes conferred protection to recipient mice subjected to IRI. Together, these results demonstrate that VNS-mediated attenuation of AKI and systemic inflammation depends on alpha 7nAChR-positive splenocytes.