Neuronal and molecular mechanisms underlying neural regulation of innate immunity

项目摘要 尽管神经生物学与免疫学研究的结合才刚刚开始，但它已经深刻地影响了 提高了我们对免疫学的理解。通过使用秀丽隐杆线虫模型系统， 确定了三种由G蛋白偶联受体介导的特异性神经免疫调节回路 OCTR-1、NPR-8和NMUR-1。我们的研究和其他研究表明， 内部免疫力的预定设定点，如人的心率的设定点，并且神经系统 系统调节免疫反应，以内部或外部环境的变化，并恢复免疫 通过将免疫力恢复到设定点来维持体内平衡。考虑到这个“免疫稳态的设定点” 理论，我们计划研究神经系统和免疫系统如何相互作用，以实现决议， 感染和先天免疫的特异性，这是免疫学中两个重要但知之甚少的问题。 以前，我们已经非常详细地描述了OCTR-1依赖的神经免疫调节回路， NMUR-1介导了C.线虫的先天免疫在这里，我们建议研究 剖析的分子和神经元机制的基础上的神经调节的决议的背景下， OCTR-1回路，并确定调节NMUR-1的特定神经元、神经网络和神经信号。 介导的先天免疫特异性。这些研究将促进我们对神经系统如何 系统控制感染消退和先天免疫特异性，并定义关键调节因子 控制神经免疫关系的原则。这些研究的结果可能有助于开发 感染性疾病和先天免疫紊乱的新疗法。

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.