Neuroimmune regulation of peripheral immune responses by modulation of food intake and energy balance

通过调节食物摄入和能量平衡来调节外周免疫反应的神经免疫

• 批准号: MR/W004623/1
• 负责人: Giuseppe D'Agostino
• 金额: $ 25.26万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW004623%2F1
• 关键词: Neuroimmune; regulation; peripheral; immune; responses

Recent advances in cross-disciplinary research have revolutionised our understanding of how the immune system is regulated by a broad range of external and internal signals that ensure optimal immunity and human health. In particular, changes in diet or availability of nutrients can have profound effects on the activity of the immune system to keep us healthy and to prevent infections, yet the mechanisms through which this is achieved remain poorly defined. The nutritional status within the body is sensed by nerve cells positioned in specific areas of the brain. By working together, these nerve cells create feelings of hunger or fullness, and in turn regulate food consumption and dietary choices by sending signals to organs throughout the body. Importantly, it is now also appreciated that many organs that play an important role for optimal immune responses are highly innervated and that many immune cells can respond directly to neurochemicals released by nerve endings. Here, we aim to investigate the hypothesis that the brain nerve cells that sense normally sense nutrient levels and control feeding activity, also possess secondary functions as direct regulators of the immune system in health and disease.In exciting preliminary findings, we found that activity of these nerve cells specifically is sufficient to drive changes in immune cell activity in a number of organs in the body. Surprisingly, many of these effects occur regardless of food consumption. Moreover, we also found that inflammation itself, on the other hand, impact on the normal way these nerve cells process food and food-related signals. In this project, we will consolidate and build on these exciting and completely new discoveries. We will make use of a wide range of cutting-edge technologies that allow us to selectivity turn discrete nerve cells in the brain on or off, as well as to visualise them in action as they are sensing nutrients. This work will be possible thanks to an existing multidisciplinary collaborative team with expertise in Neuroscience, Metabolism and Immunology. We expect that our finding will provide a solid evidence base for a previously unappreciated crosstalk between the brain mechanisms that control our feeling of hunger and fullness and the peripheral immune system, with important implications for the treatment of infectious and inflammatory disease, as well as metabolic health.

最近跨学科研究的进展彻底改变了我们对免疫系统如何受到广泛的外部和内部信号调节的理解，这些信号确保最佳免疫力和人类健康。特别是，饮食或营养素供应的变化可以对免疫系统的活动产生深远的影响，以保持我们的健康和预防感染，但实现这一目标的机制仍不明确。人体内的营养状态是由位于大脑特定区域的神经细胞感知的。通过共同工作，这些神经细胞产生饥饿感或饱足感，进而通过向全身器官发送信号来调节食物消费和饮食选择。重要的是，现在还认识到，许多对最佳免疫反应起重要作用的器官高度神经支配，许多免疫细胞可以直接对神经末梢释放的神经化学物质做出反应。在这里，我们旨在研究一种假设，即在健康和疾病中，正常感知营养水平和控制摄食活动的脑神经细胞也具有直接调节免疫系统的二级功能。在令人兴奋的初步发现中，我们发现这些神经细胞的活动足以驱动体内许多器官的免疫细胞活动的变化。令人惊讶的是，这些影响中的许多都发生在与食物摄入量无关的情况下。此外，我们还发现，另一方面，炎症本身会影响这些神经细胞处理食物和食物相关信号的正常方式。在这个项目中，我们将巩固和发展这些令人兴奋的全新发现。我们将利用广泛的尖端技术，使我们能够选择性地打开或关闭大脑中离散的神经细胞，并在它们感知营养时可视化它们的行动。由于现有的多学科合作团队在神经科学、新陈代谢和免疫学方面具有专业知识，这项工作将成为可能。我们预计，我们的发现将为控制我们饥饿感和饱腹感的大脑机制与外围免疫系统之间以前未被认识到的交叉提供坚实的证据基础，对传染病和炎症性疾病的治疗以及新陈代谢健康具有重要意义。

项目成果

Hypothalamic AgRP neurons exert top-down control on systemic TNF-a release during endotoxemia.

下丘脑 AgRP 神经元在内毒素血症期间对全身 TNF-a 释放进行自上而下的控制。

• DOI: 10.1016/j.cub.2022.09.017
• 发表时间: 2022
• 期刊: CB
• 作者: Boutagouga Boudjadja M