Reprogramming of IELs at the intestinal epithelial barrier during virus infection
Project title: Reprogramming of IELs at the intestinal epithelial barrier during virus infection
Grantor: European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie
Coordinator: dr. Špela Konjar
Prof. dr. Stipan Jonjić
Dr. Jelena Zeleznjak
Dr. Marija Mazor
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 project 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.
“This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 101027263”.