Vascular defects are present in islets during stages 1 and 2 of type 1 diabetes, when symptomatic disease has not yet developed. However, the cellular and molecular mechanisms underlying vascular dysfunction and they link with autoimmunity have not been identified. This knowledge is crucial to understand T1D pathogenesis.
In this proposal we plan to start exploring the potential involvement of pericytes in innate immune responses in islets and their functional crosstalk with macrophages in physiological and pathophysiological states. These are highly innovative topics, crucial for our understanding of how vascular homeostasis is maintained in islets and how it is disrupted in disease. Mechanistically, we plan to examine purinergic signaling in vascular and peri–vascular cells in islets at different stages of the disease. Because islet vascular alterations start in pre–symptomatic stages, elucidating the mechanisms of vascular dysfunction can shed new light into our understanding of T1D pathogenesis, and potentially reveal novel pathways/cellular players which could be targeted to delay/prevent onset.
