Neural regulation of the immune system in the Gut

ended

Maintenance of tissue health requires a variety of cellular and molecular networks. The immune system comprises panoplies of cell subsets that can sense endogenous and exogenous factors to ensure efficient surveillance and defense. Similarly, the nervous system harbors distinct neuronal populations that sense and respond to ever-changing stimuli. Interestingly, discrete neuronal and immune cells in the intestine were shown to share anatomical confinements and influence each other’s function, forming neuronal immune cell units that act as rheostats of gut physiology. Nevertheless, whether brain-derived signals control enteric immune functions and intestinal homeostasis remains elusive. Importantly, neurological dysfunction induced by stroke correlates with severe intestinal problems in humans; including infections, inflammation and colon-rectal cancer. We propose to investigate how Central Nervous System (CNS) signals control intestinal immune homeostasis and how alteration of brain-derived signals induce gastrointestinal disease. We will explore how intestinal homeostasis and immune-mediated diseases are regulated in the context of stroke, which is a major Public Health concern. To achieve this, we propose to employ genetic, cellular and molecular approaches to decipher how brain signals and pathways specifically shape gastro-intestinal immune homeostasis and what is their relevance in intestinal inflammation and cancer. To this end, stroke and gastro-intestinal disease models, together with powerful tractable, chemogenetic technology, will be employed. Astonishing preliminary data revealed that stroke severely disrupts intestinal lymphocyte homeostasis, promoting their exodus from the gut to other organs. We foresee this project as groundbreaking, establishing the link between altered brain signals and intestinal physiology, shedding light into the intricate relationships between the CNS and the gastrointestinal immune system in the context of stroke, and beyond.