Neuronal and molecular mechanisms underlying neural regulation of innate immunity

先天免疫神经调节的神经元和分子机制

• 批准号: 10680498
• 负责人: Jingru Sun
• 金额: $ 42.08万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-12 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10680498
• 关键词: Arthritis; Back; Biological Models; Caenorhabditis elegans; Development; Disease; Ensure; Failure; G-Protein-Coupled Receptors; Heart Rate; Homeostasis; Human; Immune; Immune System Diseases; Immune response; Immune system; Immunity; Immunologics; Immunology; Infection; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Innate Immune Response; Mediating; Molecular; Natural Immunity; Nervous System; Nervous System control; Neurobiology; Neuroimmune; Neurons; Research; Resolution; Sepsis; Specificity; environmental change; improved; infectious disease treatment; neural network; neuroregulation; neurotransmission; pathogen; theories

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.

项目摘要 尽管神经生物学与免疫学研究的整合刚刚开始，但它已经深刻地 提高了我们对免疫学的理解。通过使用秀丽隐杆线虫模型系统，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有一个 内部免疫力的预定设定点，例如人类心率的设定点，而神经 系统调节对内部或外部环境变化的免疫反应并恢复免疫 通过使免疫力回到设定点来体内稳态。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分辨率 感染和先天免疫学的特异性，两个重要但知之甚少的免疫学问题。 以前，我们已经表征了OCTR-1依赖性神经免疫调节电路，并且 已经揭示了NMUR-1介导了秀丽隐杆线虫先天免疫的特异性。在这里，我们提出了研究 剖析分辨率神经调节的分子和神经元机制。 OCTR-1电路并确定调节NMUR-1-的特定神经元，神经元和神经信号 介导的先天免疫特异性。这些研究将提高我们对如何紧张的理解 系统控制感染分辨率和先天免疫特异性，并定义关键调节 控制神经免疫关系的原则。这些研究的结果可能有益于发展 传染病和先天免疫疾病的新疗法。