A humanized T cell mouse model to study pathobionts in IBD

Inflammatory Bowel Disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) is caused by environmental triggers and a dysregulated immune system. Interactions between certain bacteria, known as pathobionts, and the gut immune system contribute to IBD in animal models. However, we understand little of the types of pathobionts that might be influencing human IBD. This project aims to generate a humanized mouse model engineered with a human T cell antigen recognition system (VelociT mouse from Regeneron) and human gut microbiota. Establishment of a colitis model induced by microbiota-dependent immune dysregulation will mimic pathogenesis in human IBD patients. These mice can be used for identification of the yet unknown IBD-related pathobiont(s) and understanding how the pathobionts interact with the immune cells. One major advantage of our model is that the humanized mice express a diverse set of the HLA alleles which allows them to be matched to patients with the same HLA alleles, allowing for patient-specific analysis and potentially testing of personalized therapies in the future. This model will help investigate the triggers of human disease development and bridge the gap between animal models and clinical IBD research, contributing significantly to better understanding of IBD pathogenesis.