Figure 1.

Isogenic modeling facilitates the investigation of multiple cell types important in the pathogenesis of type 1 diabetes (T1D). A combination of environmental and genetic factors influences the overall risk for T1D. Genes conferring risk for T1D may affect the functions of β cells, immune cells, and vascular endothelium. For β cells, risk variants of some genes may alter the response to environmental triggers such as inflammatory or viral sensing, or they may alter the way that β cells cope with stress from bioenergetic demands. For immune cells, gene variants my alter the way that T and B cells are selected in primary (1°) lymphatic tissues during central tolerance, or they may alter several key events that occur during antigen-specific priming and effector differentiation in the peripheral (2°) lymphatics. Immune destruction of β cells requires homing of innate and adaptive effector populations into the pancreatic islets, so alterations to endothelial function could affect disease at this late stage. Isogenic cellular modeling can be applied to complex multifactorial diseases to facilitate a more complete understanding of which genes are expressed in any given tissue/cell type and at which developmental stage they may exert their influence on disease progression.