Investigating the Role of Tissue resident memory T Cells and Interleukin-7 in the Transition from Acute Inflammation to Chronic Mucosal Damage in Crohn’s Disease

• Applicant: Dr. Annerose Eleonore Ziegler
• Subject Area: Gastroenterology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 569322949

Crohn’s disease (CD) is an autoimmune-mediated inflammatory bowel disease (IBD) that can affect the entire gastrointestinal tract and lead to chronic inflammation. Pathogens such as enteric virus infections have been implicated as environmental triggers that initiate and sustain chronic inflammation, highlighting their role as potential catalysts for disease exacerbations. While rotavirus (RV) is not typically identified as a trigger for IBD flares, in seropositive patients, the virus may be cleared quickly, and as a result, subsequent diagnostic tests fail to detect it. Consequently, the infection as a potential trigger for an IBD flare might not be identified. Understanding immune-stromal-epithelial interactions within the intestinal microenvironment is crucial for unraveling the complexities of IBD pathology. We hypothesize that IL-7 plays a pivotal role in transitioning acute inflammation into chronic mucosal damage following enteric virus infections in IBD, with TRM cells as key mediators. To investigate this, we will use ileal air liquid interface (ALI) organoids to model RV-induced epithelial infection and immune activation, aiming to elucidate how enteric viral infections contribute to inflammation and impair mucosal healing in IBD. Specifically, this research will examine how IL-7-mediated immune responses following viral infection disrupt epithelial integrity and promote chronic inflammation, shedding light on the role of viral infections in CD flares. Since RV primarily infects the small intestine and CD - while affecting the entire gastrointestinal tract – frequently leads to terminal ileitis, this study will focus on ALI organoids derived from ileal biopsies and their relevance to CD. By leveraging ileal ALI organoid models, we can uncover the mechanisms by which enteric viral infections contribute to IBD, offering potential targets for future therapeutic development. Specifically, it will decipher how IL-7-mediated immune responses disrupt epithelial integrity and perpetuate chronic inflammation. The findings will clarify the interplay between infections and CD flares and might identify novel therapeutic targets preventing the transition from acute inflammation into chronic tissue damage.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Dr. Calvin Kuo, Ph.D.