Neuronal and molecular mechanisms underlying neural regulation of innate immunity

项目摘要 虽然神经生物学与免疫学研究的结合才刚刚开始，但它已经深刻地 提高了我们对免疫学的理解。通过使用秀丽线虫模型系统，我们有 确定了由G蛋白偶联受体介导的三个特定的神经免疫调节回路 OCTR-1、NPR-8和NMUR-1。我们的研究和其他研究表明，可能存在一种 体内免疫力的预先设定的设定点，就像人类心率的设定点，以及神经质 系统调节对内部或外部环境变化的免疫反应，并恢复免疫 通过将免疫力恢复到设定点来实现动态平衡。考虑到这个“免疫动态平衡的设定点” 理论上，我们计划研究神经系统和免疫系统如何相互作用来实现对 感染和先天免疫的特异性是免疫学中两个重要但知之甚少的问题。 此前，我们已经非常详细地描述了OCTR-1依赖的神经免疫调节电路和 已发现NMUR-1介导线虫天然免疫的特异性。在这里，我们建议进行研究 剖析神经调节分辨率的分子和神经元机制。 OCTR-1电路并识别调节NMUR-1的特定神经元、神经网络和神经信号- 天然免疫的介导性特异性。这些研究将增进我们对神经质是如何 系统控制感染解决方案和先天免疫特异性，并定义关键调节 管理神经免疫关系的原则。这些研究的结果可能有助于该研究的发展 传染病和先天免疫疾病的新疗法。

Project Summary Although the integration of neurobiology into immunological research has just begun, it has already profoundly improved our understanding of immunology. By using the Caenorhabditis elegans model system, we have identified three specific neuro-immune regulatory circuits that are mediated by the G protein-coupled receptors OCTR-1, NPR-8, and NMUR-1, respectively. Our studies and others indicate that there could be a predetermined setpoint for internal immunity, like the setpoint for the human heart rate, and that the nervous system regulates immune responses to internal or external environmental changes and restores immune homeostasis by bringing immunity back to the setpoint. Considering this “setpoint for immune homeostasis” theory, we plan to investigate how the nervous system and immune system interact to achieve the resolution of infection and the specificity of innate immunity, two important but poorly understood issues in immunology. Previously, we have characterized the OCTR-1-dependent neuro-immune regulatory circuit in great detail and have revealed that NMUR-1 mediates the specificity of C. elegans innate immunity. Here, we propose studies to dissect the molecular and neuronal mechanisms underlying neural regulation of resolution in the context of the OCTR-1 circuit and to identify specific neurons, neural networks, and neural signals that regulate NMUR-1- mediated specificity of innate immunity. These studies will advance our understanding of how the nervous system controls both infection resolution and innate immune specificity as well as define key regulatory principles that govern neuro-immune relationships. Results from these studies could benefit the development of new treatments for infectious diseases and innate immune disorders.