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Neural regulation of the immune system in the Gut

Project description

Towards a better understanding of the complex brain–gut connection

Some neuronal and immune cells in the intestine share anatomical features and influence each other's function, forming neuronal–immune cell units. However, whether brain-derived signals might control enteric immune functions and intestinal homeostasis has not been adequately studied. Curiously, the neurological dysfunction induced by stroke is associated with intestinal problems, including infections, inflammation and colorectal cancer. The promising preliminary data has demonstrated that stroke disrupts intestinal lymphocyte homeostasis, promoting their release from the gut to other organs. The EU-funded Neu-i-Gut project will investigate how the central nervous system affects intestinal immune homeostasis and whether brain-derived signals induce gastrointestinal disease. To that end, researchers will employ stroke and gastrointestinal disease models, together with genetic technology.

Objective

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.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2018

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Coordinator

FUNDACAO D. ANNA DE SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 159 815,04
Address
AVENIDA BRASILIA, CENTRO DE INVESTIGACAO DA FUNDACAO CHAMPALIMAUD
1400-038 LISBOA
Portugal

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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 159 815,04
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