Grant: Operating Grant

In the past decade, childhood type 1 diabetes that is now generally referred as type 1 diabetes (T1D) has increased dramatically worldwide and has almost reached endemic proportions. However the mechanisms underlying diabetes onset remain poorly understood. Whereas basic and clinical research aim at understanding the causes that lead to diabetes, along with therapies to improve managing, are somewhat limited in human diabetic patients from several angles. Fortunately, animal models are available, and this is the case of the non-obese diabetic (NOD) mouse that has become invaluable for studies on diabetes. NOD mice spontaneously develop T1D, and many characteristics of diabetes in these mice mirror features of the chain of events that lead to development of diabetes in humans. Of significance, a large body of knowledge with respect to regulation of immune responses in NOD mice is known. Furthermore, NOD mice can be genetically modified to address specific immune aspects of diabetes. For instance, specialized cells called dendritic cells (DCs) act to dampen unwanted immune responses and promote a specialized white blood cell (named regulatory T cells: Treg) function in order to prevent diseases onset. Abnormal function of DCs has been reported to play a critical role in initiation and progression of type 1 diabetes. Many proteins influence the normal set-point of DCs. Recent research indicates that augmenting the function of a protein called Stat5b leads to increased numbers of beneficial specialized white blood cells (Treg) in mice. Our proposal seeks to determine if correcting Stat5b protein function expressed in DCs can suppress development of juvenile diabetes in a well-characterized NOD mouse model. If successful, this approach may spur the development of new therapies for patients suffering from childhood type 1 diabetes.