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Neural regulation of the immune system in the Gut

Descrizione del progetto

Verso una migliore comprensione del complesso collegamento cervello-intestino

Alcune cellule neuronali e immunitarie nell’intestino condividono le caratteristiche anatomiche e influenzano la reciproca funzionalità, formando unità cellulari neuro-immunitarie. Non è stato tuttavia adeguatamente studiato se i segnali derivati dal cervello possano controllare le funzioni immunitarie enteriche e l’omeostasi intestinale. Curiosamente, la disfunzione neurologica indotta dall’ictus si associa a problemi intestinali, quali infezioni, infiammazioni e cancro del colon-retto. I promettenti dati preliminari hanno dimostrato che l’ictus altera l’omeostasi dei linfociti intestinali, favorendone il rilascio dall’intestino verso altri organi. Il progetto Neu-i-Gut, finanziato dall’UE, studierà in che modo il sistema nervoso centrale influisce sull’omeostasi immunitaria intestinale e se i segnali derivati dal cervello inducono malattie gastrointestinali. A tal fine, i ricercatori utilizzeranno modelli di ictus e malattie gastrointestinali, insieme alla tecnologia genetica.

Obiettivo

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.

Campo scientifico (EuroSciVoc)

CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP.

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Coordinatore

FUNDACAO D. ANNA DE SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Contribution nette de l'UE
€ 159 815,04
Indirizzo
AVENIDA BRASILIA, CENTRO DE INVESTIGACAO DA FUNDACAO CHAMPALIMAUD
1400-038 Lisboa
Portogallo

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Tipo di attività
Research Organisations
Collegamenti
Costo totale
€ 159 815,04