Intercellular Arc Signaling Regulates Vasodilation
Intercellular Arc Signaling Regulates Vasodilation
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DOI：
10.1523/jneurosci.0440-21.2021
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发表时间：
2021-09-15
影响因子：
5.3
通讯作者：
Campbell, Zachary T.
中科院分区：
文献类型：
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作者：
de la Pena, June Bryan;Barragan-Iglesias, Paulino;Campbell, Zachary T.
损伤反应需要皮肤中不同细胞类型之间的沟通。感觉神经元会导致炎症，并能分泌影响非神经元细胞的信号分子。尽管翻译调节在伤害感受中发挥着普遍作用，但活性依赖性蛋白质合成对炎症的贡献尚不清楚。为了解决这个问题，我们使用核糖体分析检查了用炎症介质处理的小鼠背根神经节（DRG）神经元的新生翻译情况。我们确定了活性依赖性基因 Arc 作为体外和体内翻译的靶标。炎症信号促进电弧在皮肤中的局部翻译。电弧缺陷的雄性小鼠在应对炎症挑战时表现出过高的爪子温度和血管舒张。由于 Arc 最近被证明是从细胞外囊泡 (EV) 中的神经元释放的，因此我们假设细胞间 Arc 信号传导调节皮肤的炎症反应。我们发现，在 Arc 缺陷小鼠中观察到的过度热反应和血管舒张可以通过将含有 Arc 的 EV 注射到皮肤中来缓解。我们的研究结果表明，传入纤维中 Arc 的活动依赖性产生可能通过细胞间信号传导调节神经源性炎症。
Injury responses require communication between different cell types in the skin. Sensory neurons contribute to inflammation and can secrete signaling molecules that affect non-neuronal cells. Despite the pervasive role of translational regulation in nociception, the contribution of activity-dependent protein synthesis to inflammation is not well understood. To address this problem, we examined the landscape of nascent translation in murine dorsal root ganglion (DRG) neurons treated with inflammatory mediators using ribosome profiling. We identified the activity-dependent gene, Arc, as a target of translation in vitro and in vivo. Inflammatory cues promote local translation of Arc in the skin. Arc-deficient male mice display exaggerated paw temperatures and vasodilation in response to an inflammatory challenge. Since Arc has recently been shown to be released from neurons in extracellular vesicles (EVs), we hypothesized that intercellular Arc signaling regulates the inflammatory response in skin. We found that the excessive thermal responses and vasodilation observed in Arc defective mice are rescued by injection of Arc-containing EVs into the skin. Our findings suggest that activity-dependent production of Arc in afferent fibers regulates neurogenic inflammation potentially through intercellular signaling.