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

点击翻译按钮获取中文摘要

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.