Modeling Type 1 Diabetes In Vitro Using Human Pluripotent Stem Cells

Understanding the root causes of autoimmune diseases is hampered by the inability to access relevant human tissues and identify the time of disease onset. To examine the interaction of immune cells and their cellular targets in type 1 diabetes, we differentiated human induced pluripotent stem cells into pancreatic endocrine cells, including β cells. Here, we describe an in vitro platform that models features of human type 1 diabetes using stress-induced patient-derived endocrine cells and autologous immune cells. We demonstrate a cell-type-specific response by autologous immune cells against induced pluripotent stem cell-derived β cells, along with a reduced effect on α cells. This approach represents a path to developing disease models that use patient-derived cells to predict the outcome of an autoimmune response. [Display omitted] •β cell-specific response is achieved using iPSC-β cells and autologous immune cells•An in vitro immune response to iPSC-β cells requires ER stress•T cell activation is restricted to autologous iPSC-β cells•T cell activation is mediated by TCR engagement of peptide-HLA complexes on iPSC-β Leite et al. describe an in vitro platform that models features of autoimmune type 1 diabetes using patient-derived endocrine cells and autologous immune cells. This represents a path to developing a model with patient-derived cells to predict and analyze the autoimmune response.