Beyond inflammation: Organoid models of epithelial stem cell reprogramming in IBD

Inflammatory bowel disease (IBD) has traditionally been viewed as a disorder driven by chronic immune-mediated inflammation. However, successful mucosal healing depends on the ability of the intestinal epithelium to regenerate following injury.

Our work has identified epithelial stem cell reprogramming as a central process linking inflammatory signalling to tissue repair. Using patient-derived organoids, murine models, spatial transcriptomics, and single-cell approaches, we have shown that inflammatory mediators, including TNF and Type I interferons, regulate epithelial stem cell behaviour through coordinated interactions with the mesenchymal niche. These pathways determine whether inflammation promotes effective regeneration or contributes to persistent barrier dysfunction and failure to respond to therapy.

This seminar will present recent findings that redefine inflammatory signalling as both a driver of tissue damage and a regulator of epithelial repair, highlighting new opportunities to develop regenerative therapies and biomarkers for patients with IBD.