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

跨学科研究的最新进展彻底改变了我们对免疫系统如何受广泛的外部和内部信号调节的理解，这些信号确保了最佳的免疫力和人体健康。特别是，饮食或营养物质的变化会对免疫系统的活动产生深远的影响，从而保持我们的健康和预防感染，但实现这一目标的机制仍不清楚。身体内的营养状况由位于大脑特定区域的神经细胞感知。通过共同努力，这些神经细胞产生饥饿感或饱腹感，并通过向全身器官发送信号来调节食物消耗和饮食选择。重要的是，现在也认识到许多对最佳免疫反应起重要作用的器官是高度神经支配的，许多免疫细胞可以直接对神经末梢释放的神经化学物质作出反应。在这里，我们的目的是研究一种假设，即正常感知营养水平和控制摄食活动的脑神经细胞，在健康和疾病中也具有作为免疫系统直接调节器的次要功能。在令人兴奋的初步发现中，我们发现这些神经细胞的活性足以驱动身体许多器官中免疫细胞活性的变化。令人惊讶的是，许多这些影响与食物摄入无关。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，我们将巩固和建立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将它们的活动可视化。由于现有的多学科合作团队具有神经科学、代谢和免疫学方面的专业知识，这项工作将成为可能。我们期望我们的发现将为控制我们的饥饿感和饱腹感的大脑机制与外周免疫系统之间的相互作用提供坚实的证据基础，对感染性和炎症性疾病的治疗以及代谢健康具有重要意义。

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.