The role of IL-1ra in type 1 diabetes

In our preliminary studies, we identified a new biomarker that can predict the onset of islet autoantibodies and type 1 diabetes (T1D). This new biomarker is a serum protein, known as IL-1ra, which plays a critical role in controlling the pro-inflammatory response and beta cell destruction. This proposal will continue our exciting research on the predictive value of IL-1ra and investigate its role in diabetes development. The proposal contains three specific aims. First, we will measure IL-1ra in the serum of the entire DIASY cohort (2449 children) that has been studied for 17 years. These children were identified to be at high risk based on their HLA genes and have been monitored for the development of islet autoantibodies and T1D. Studies of these ~25,000 serum samples from these children will allow us to precisely define the likelihood of becoming islet autoantibody-positive and diabetic based on the levels of serum IL-1ra, thus providing necessary data on how to use serum IL-1ra to predict diabetes. Second. We will use modern technologies to examine how IL-1ra changes the gene expression and function of immune cells and beta cells. These studies will allow us to better understand the role of IL-1ra in regulating immune response and prevention of beta cell destruction, thus providing new ways for disease prevention. Finally, we will investigate in mice deficient for IL-1ra to understand how IL-1ra deficiency may lead to the development of islet autoimmunity and diabetes.