Optimizing antigen-specific immunotherapy in type 1 diabetes.

Antigen (Ag)-specific immunomodulatory strategies aimed at the induction of self-tolerance are alluring approaches to safely prevent and treat organ-specific autoimmune diseases like type 1 diabetes (T1D). Here, we build on previous data demonstrating that a new bacterial system for delivering beta-cell autoAgs along with immunomodulators to the gut can interfere with the process of diabetes in NOD mice, a model of human T1D. By this project, we want study in more detail how this Ag-specific therapy allows for the specific tolerization of self-reactive immune cells, while maintaining the immune systems ability to clear non-self Ags.

Our studies will involve state-of-the-art in vitro and in vivo immune experiments to elucidate the mechanisms of action by which diabetes treatment can be induced. Moreover, we will fine-tune and improve on the therapeutic efficacy of our current therapy by adding more subtle immunomodulatory, anti-inflammatory and beta-cell protective/regenerative agents to effectively preserve/restore beta-cell function in recent onset diabetic mice. We are positive that our project holds great promise for the T1D field as the proposed interventions are Ag-specific, less invasive, carry low toxicity risk, and are therefore very close to the clinic.