Type 1 diabetes (T1D) is an autoimmune disease, where immune cells (T cells) of the body attack and destroy the insulin-producing beta cells. T1D is, if left untreated, a devastating and life-threatening disease and despite intensive research in the field, there are still missing pieces in the pathogenetic puzzle of the disease. With this project, we plan to focus on the innate immune system and its role in the development of T1D. Innate immune cells, mainly represented here by macrophages (ΜΦ) and dendritic cells (DCs), are among the earliest responders to inflammation, infection and stress, yet their direct implication in the development of T1D remains unknown in humans. We propose to investigate the type, distribution, and main function of these innate immune cells in the human pancreas, by defining them based on their unique markers.

By the end of this project, we expect to define the innate immune cell landscape and the changes that might take place as T1D progresses. Furthermore we will use specialized in vitro experiments, live cell- and 3D-imaging as well as super resolution microscopy, and transcriptomic and proteomic assays to study islet-immune cell interactions and beta cell function. Our goal is to better define the role of innate immune cells in the pathogenesis of T1D by acquiring quantitative data from human pancreata. In addition, we aim to obtain mechanistic information from in vitro experiments to understand how innate immune cells interact with beta cells. This will allow us to identify new “players” in the pathogenesis of T1D that will serve as targets for pharmacological intervention, bringing us closer to the prevention and cure of T1D.