Neural code of the immune responses

免疫反应的神经密码

• 批准号: 10223196
• 负责人: Jonathan Kipnis
• 金额: $ 110.25万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-18 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10223196
• 关键词: Brain; Cells; Code; Communication; Disease; Environment; Immune; Immune response; Immune system; Immunity; Immunologics; Integrative Therapy; Mediating; Meningeal lymphatic system; Meninges; Neuroimmune; Neurologic Symptoms; Role; Route; Stimulus; System; Testing; brain circuitry; connectome; lymphatic vessel; microorganism; neuroimmunology; pathogen; relating to nervous system; response

Neuroimmunology studies communication between the nervous and the immune systems – arguably among the most complicated systems of our body. We have demonstrated that the two systems are closely integrated unlike what was previously assumed and have identified the meninges as the place through which immune cells mediate their effect. We have also (re)discovered meningeal lymphatic vessels and demonstrated that these vessels serve as a communication route between the brain and immunity. The brain is our computing machine that integrates stimuli from the environment and orchestrates responses to these stimuli. But we have evolved and live in the world of microorganisms. It is unconceivable to imagine that the brain would give up on ‘sensing’ the microorganisms. In this proposal, we will test the hypothesis that the defining role of the immune system is to sense microorganisms and inform the brain about them. We propose that the immune responses are hardwired within our brain with connections to numerous circuits. These connections create a “neuroimmune connectome”, altering which interferes with brain function. We will concentrate our efforts to decipher the neuroimmune connectome, to unravel the mechanism through which immune cells inform the brain of commensals and pathogens, and understand the consequences of brain’s response to immunological ‘information’. Understanding immune inputs into brain circuitry could be the key to understanding neurological manifestations of diseases impacted by the immune system as well as the mechanisms of actions underlying the impacts of conventional and complementary/integrative therapies on diseases.

神经免疫学研究神经系统和免疫系统之间的通信-可以说是我们身体中最复杂的系统之一。我们已经证明，这两个系统是紧密结合的，不像以前假设的那样，并且已经确定脑膜是免疫细胞介导其作用的地方。我们还（重新）发现了脑膜淋巴管，并证明这些血管是大脑和免疫系统之间的沟通途径。 大脑是我们的计算机器，它整合来自环境的刺激并协调对这些刺激的反应。但我们已经进化并生活在微生物的世界里。很难想象大脑会放弃“感知”微生物。在这个提议中，我们将测试免疫系统的定义作用是感知微生物并将其告知大脑的假设。我们认为，免疫反应在我们的大脑中与许多回路相连。这些连接创造了一个“神经免疫连接体”，改变它会干扰大脑功能。我们将集中我们的努力来破译神经免疫连接体，解开免疫细胞通知大脑的病原体和病原体的机制，并了解大脑对免疫“信息”的反应的后果。了解进入大脑回路的免疫输入可能是理解受免疫系统影响的疾病的神经学表现以及传统和补充/综合疗法对疾病影响的作用机制的关键。