Identification of a new pathway that restrains repair during colitis

Inflammatory Bowel Diseases (IBD) are a devastating group of heterogenous inflammatory diseases that share the fact that the host immune system attacks the intestinal tissue disrupting gut functionality. All therapies currently available, such as biologics, target immune mediators that support damage and inflammation. Although these therapies ameliorated the life of many IBD patients, they not always work or stop to work overtime, highlighting the urgent need to develop new therapeutic approaches. Here, we propose to complement therapeutic interventions aimed at decreasing immune attack and intestinal damage by identifying new strategies that can be utilized to favor gut repair. In particular, we identified a new transcriptional program in intestinal epithelial cells that can be harnessed to facilitate intestinal healing. In our application we propose multiple studies based on: i) mouse models of colitis to test new therapeutic approaches; ii) human and mouse organoids to mimic intestinal epithelial cell damage and repair; and iii) use of biopsies from IBD patients and analysis of large human datasets to translate our findings to IBD patients. Our studies will reveal new therapeutic targets and strategies aimed at fostering tissue repair. These new interventions can be utilized in conjunction with current anti-inflammatory therapies to facilitate gut healing, thus ameliorating the quality of life of IBD patients.