The role of type 2 innate lymphoid cells in autoimmune islet infiltration and diabetes

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Type 1 diabetes is an increasing problem in the UK and worldwide, with rising numbers of people being affected year on year. The underlying problem is that the immune system attacks and destroys the cells that make insulin in the pancreas. We know that a type of immune cell called a T-cell is responsible for driving the process, however it does not work alone: coordinated interaction between a number of different cell types is required. Understanding the contribution of these different cell types to the disease process is vital for us to design ways to interfere with the immune-mediated attack in an informed way.While analysing the immune cells infiltrating the pancreas in autoimmune diabetes, we recently discovered a population that has not been reported here before. These so called "Innate Lymphoid Cells" or ILC are relative newcomers to the field but have generated lots of excitement over the last few years. They are rare cells, but appear capable of profoundly influencing immune responses - i.e. they punch above their weight. It has been shown that they can change the way T-cells behave, instructing them to secrete different products and alter the type of immune response that is occurring. We have very recent data showing that they can alter whether T-cells secrete something called IL-21 which we know is linked to the development of type 1 diabetes. It is therefore possible that ILC play a key role in determining whether a destructive immune response against the pancreas is mounted.At present nothing is known about the role of ILC in type 1 diabetes since the area is completely uninvestigated. Our proposed experiments will define how ILC affect T-cells during the initiation of an immune response in the pancreas, and in turn how the T-cells influence the ILCs themselves. We will use clues from our preliminary data, and the latest discoveries from the ILC field, to ask questions about whether ILC respond to dying pancreas cells or interact with nervous system components. By collaborating with leading experts in ILC biology, we will perform experiments to directly test whether ILC influence diabetes induction or progression. Importantly, some of the treatments being developed for autoimmune diseases like type 1 diabetes are likely to act on ILC as well as T-cells. It is therefore vital to understand whether ILC play a positive or negative role in disease development so that these drugs can be used correctly.Collectively this project will build on exciting new data from our group to define the role of a new player in the immune-mediated attack on the pancreas.