Project Details
Projekt
Identifying Novel Therapeutic Targets for Inflammatory Bowel Disease Using Large Scale Immune Repertoire Profiling of Gut Tissues
Subject Area
Gastroenterology
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 579974334
Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammation of the digestive tract. While the exact cause of IBD remains to be elucidated, dysregulated immune responses toward the microbiome, the mycobiome, and common infections such as EBV have been observed in individuals with IBD. Using large-scale T cell repertoire profiling across thousands of individuals with IBD, we identified and validated hundreds of clonotypes implicated in the disease. Nonetheless, the exact mechanisms by which these T cell clones drive the disease remain unclear, specifically, their spatial distribution across different sections of the gut, the impact of inflammation on their expansion, and their transcriptomic and epigenomic profiles. Our project aims to address this knowledge gap by studying the T cell repertoire in different parts of the intestine in treatment-naïve individuals with IBD and in matching symptomatic controls, i.e., individuals with symptoms of IBD whose endoscopy and laboratory tests did not allow an unambiguous diagnosis of CD or UC. Furthermore, we will compare the repertoires of samples collected at the treatment-naïve stage with paired samples collected from the same individuals one year after treatment. This will enable us to decode the effects of therapy on the composition of gut-resident T cells and, consequently, to develop prognostic markers to predict therapy response. This project will use a unique patient cohort from Norway (IBSEN-III), which provides access to tissue biopsies collected at diagnosis, before treatment, and again during follow-up. This rare resource allows us to compare immune responses in untreated and treated patients, in both responders and non-responders to therapy. We will also apply state-of-the-art single-cell methods to examine the activity and regulation of individual disease-associated T cells, providing insights into how they contribute to ongoing inflammation. The outcome of this research will be a detailed atlas of T cell distributions in the gut and a refined list of disease-associated T cells that can serve as potential therapeutic targets. In the long term, this knowledge could guide the development of new immunotherapies, such as targeted removal of harmful T cells or vaccines that retrain the immune system, to improve treatment outcomes and the quality-of-life for people living with IBD.
DFG Programme
Research Grants
