Neural code of the immune responses

免疫反应的神经密码

基本信息

批准号：
10218743
负责人：
Jonathan Kipnis
金额：
$ 110.25万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
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

项目摘要

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讯——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，与之前的假设不同，并且已经确定脑膜是免疫细胞介导其功能的地方。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之间的沟通途径。大脑是我们的计算机，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中，很难想象大脑会放弃“感知”微生物。在这个提议中，我们将检验这样的假设：免疫系统的决定性作用是感知微生物并向大脑通报它们的情况。我们认为，免疫反应是与我们的大脑内部的许多电路相连的。我们将集中精力破译神经免疫连接组，揭示免疫细胞向大脑通报共生体和病原体的机制，并了解大脑对免疫反应的后果。了解大脑回路的免疫输入可能是了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。