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...
ver más
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Información proyecto Neu-i-Gut
Duración del proyecto: 41 meses
Fecha Inicio: 2019-03-22
Fecha Fin: 2022-08-31
Fecha límite de participación
Sin fecha límite de participación.
Descripción del proyecto
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.