Type I diabetes (T1D) is an autoimmune disease that can be managed, but for which there is currently no cure. Recent discoveries, particularly in mouse models, indicate that targeted modulation of the immune response has the potential to move an individual from a diabetic to a long-term, if not permanent, healthy state. In this paper we develop a single compartment mathematical model that captures the dynamics of dendritic cells (DC and tDC), T cells (effector and regulatory), and macrophages in the development of type I diabetes. The model supports the hypothesis that differences in macrophage clearance rates play a significant role in determining whether or not an individual is likely to become diabetic subsequent to a significant immune challenge. With this model we are able to explore the effects of strengthening the anti-inflammatory component of the immune system in a vulnerable individual. Simulations indicate that there are windows of opportunity in which treatment intervention is more likely to be beneficial in protecting an individual from entering a diabetic state. This model framework can be used as a foundation for modeling future T1D treatments as they are developed.
Keywords: immunotherapy; macrophage clearance; mathematical model; regulatory T cells; tolerogenic dendritic cells; treatment simulation; type I diabetes.