'Modelling autoimmunity - Novel system of human intestinal organoids recapitulate Celiac Disease' by Dr Antonio Santos

This seminar is open to members of the University of Oxford only. Please register with your University of Oxford email to ensure a successful registration. Registration is at: https://medsci.zoom.us/meeting/register/tJEqfuGsrT4pHdAbctWRou9PREHtRw2vlQG0

Celiac disease (CeD) is a common and potentially disabling autoimmune disorder where dietary gluten-derived peptides initiate immune-mediated small intestinal mucosal injury, but human experimental models have been elusive. Many human in vitro models of autoimmunity have been constrained by an inability to culture affected epithelium alongside the complex tissue-resident immune microenvironment. As a post-doc in the Kuo lab (Stanford University) I successfully generated a novel human small intestinal organoid system using an air-liquid interface (ALI) that robustly preserves epithelium alongside native mesenchyme and diverse tissue-resident immune cells, including T, B and myeloid cells. Notably in ALI organoids from CeD patients but not controls, MHC class II-restricted gluten peptides stimulate epithelial killing and activate and expand gluten-specific T cells, leading to cytokine upregulation and subsequent production of B cell autoantibodies. This novel intestinal organoid system has provided new insight into the complex immune-epithelial network that occurs in CeD, establishing proof-of-principle for general organoid modelling of antigen-driven immunity.