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Reprogramming of IELs at the intestinal epithelial barrier during virus infection

Project description

Immune responses at the intestine after virus infection

CD8+ T cells, also known as cytotoxic T cells, have a key role in immune responses against viruses and can either circulate in the body or reside in specific tissues such as the intestine. Apart from eliminating infected cells, intraepithelial lymphocytes (IELs) in the intestine have an emerging role in intestinal pathology, for example in inflammatory bowel disease. The EU-funded Virus RePro IEL project aims to understand how viruses affect IELs at the intestinal epithelial barrier. Researchers will employ cutting-edge sequencing methodology to determine gene expression changes following virus infection and delineate the impact of external factors such as a high-fat diet and antibiotics on IELs

Objective

Intestinal epithelial resident CD8+ T lymphocytes, such as intraepithelial lymphocytes (IELs), are located at epithelial barriers. They play a key role in tissue protection by promoting the elimination of infected cells, while producing antimicrobial factors and epithelial growth factor. Due to the positioning of IELs underneath the single epithelial layer and their potential involvement in modulating intestinal pathology, the activation status of IELs is intensively studied.
Viruses modify CD8 T cells in many ways. Murine cytomegalovirus (MCMV) belongs to β-herpesviruses and is often used as an animal model to study the pathogenesis of human cytomegalovirus (HCMV). MCMV specific resident memory CD8 T cells has been described in intestine. Memory CD8 T-cell in the gut epithelium induced by persistent viruses such as MCMV has a distinct quality from both conventional memory and “inflationary” memory CD8 T cells, which may be relevant to protection against mucosal infections. The outcome for patients with HCMV reactivation appears worse than for patients without reactivation. It is not absolutely clear whether HCMV is a contributor or a bystander cause of inflammatory bowel disease (IBD).
In this proposal we aim to define the possible mechanisms by which virus impact IELs at the intestinal epithelial barrier in comparison to virus impact on circulating CD8 , and how they then behave in different challenges to which intestine could be exposed such as DSS triggered colitis, antibiotic treatment and high fat diet. For this, we will use sequencing approaches and data analysis of gene in different conditions in IELs. How the IELs “reprogram” their gene composition due to combination of the challenges will be our main goal additionally to classical approaches to with the immunological and biochemistry techniques. These findings can potentially lead to new diagnostic methods and therapeutic targets in mucosal conditions that are major public health burden.

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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-2020

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Coordinator

SVEUCILISTE U RIJECI, MEDICINSKI FAKULTET
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.

€ 147 463,68
Address
BRACE BRANCHETTA 20
51000 Rijeka
Croatia

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Region
Hrvatska Jadranska Hrvatska Primorsko-goranska županija
Activity type
Higher or Secondary Education Establishments
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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.

€ 147 463,68
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