Inflammatory bowel disease (IBD) is a debilitating chronic gastrointestinal condition resulting from an immune overreaction against microbiota. Intermittent inflammatory flares damage the gut and despite the cells’ efforts to repair the tissue and anti-inflammatory treatments, cellular programmes become altered over time. During IBD, fibroblasts – the main cells promoting wound healing – adopt a pro-inflammatory phenotype and secrete excessive extracellular matrix components, while epithelial cells trans-differentiate to acquire fibroblast-like properties. In addition, neurons modify their membrane potentials. Eventually, severe untreatable complications such as intestinal fibrosis, gut dysmotility and chronic pain appear. Therefore, understanding IBD pathomechanisms is a clinical unmet need.
To comprehend intestinal fibrosis, we isolate primary intestinal epithelial cells and fibroblasts from mice to induce IBD-relevant damage in vitro and characterize their phenotype (wound healing and contractibility assays, collagen secretion, IF, western blot, etc), and crosstalk (RNA-seq, confocal microscopy). Complementarily, we induce experimental colitis in genetically-modified mice lacking the expression of a DNA methyltransferase that seems crucial for fibrosis in epithelial cells or fibroblasts, or lacking the expression of key IBD autophagy and ER stress genes in neurons.
