Fibrogenic Mechanisms in Inflammatory Bowel Diseases

Fibrosis is a serious yet underappreciated complication of inflammatory bowel disease (IBD). The excessive extracellular matrix deposition and replacement of epithelial tissue by mesenchyme during fibrosis impairs the absorptive function and can lead to fibrotic stenosis requiring surgery. Although inflammation initiates fibrosis, anti-cytokine therapies fail to halt its progression, indicating persistent fibrogenic mechanisms even after inflammation subsides. Single-cell RNA sequencing of affected colon tissues identified fibroblasts as the most altered cell population during IBD. As key mediators of injury response, deregulated fibroblast function leads to fibrosis. However, the fibroblast functions that dictate fibrosis versus mucosal healing, and how these cells interact with other cell types in the affected tissue, remain unclear. Understanding these functional changes is key to guiding the development of targeted anti-fibrotic therapies in IBD.