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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- medical and health scienceshealth sciencespublic health
- natural sciencesbiological sciencesmicrobiologyvirology
- medical and health sciencesclinical medicinegastroenterologyinflammatory bowel disease
- medical and health scienceshealth sciencesnutrition
- medical and health sciencesbasic medicinepathology
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Keywords
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
51000 Rijeka
Croatia