Spatio-temporal dynamics of insulitis in human type 1 diabetes
Type 1 diabetes is a chronic autoimmune disease characterised by the selective destruction of pancreatic beta cells. The disease, which currently has no cure, affects around 400,000 people in the UK, and is the more common form of diabetes in children, of whom as many as 30,000 have the illness in Britain. This requires life-long insulin administration and is associated with a significant reduction in life expectancy and quality of life.
Heavily implicated as the main cause of type 1 diabetes are the T-lymphocytes, which are thought to be directly responsible for beta cell death. Other immune cells, such as B-lymphocytes and macrophages are also present during insulitis, though their role is less well understood. Novel results from our collaborators, Prof. Morgan and his team, have identified two phenotypes of the disease: an aggressive phenotype characterised by high numbers of B-lymphocytes and a more passive phenotype involving fewer B-lymphocytes.
Previous modelling approaches have ignored the important spatial aspects of the disease progression, together with its inherent heterogeneity. By modelling the problem as an agent-based system, we address these issues and study the emergent behaviour of a system of immune and beta cells following a simple set of biophysically plausible rules. In particular, this project focuses on the role of communication between different immune cell types and how this results in a coordinated attack on the beta cells.
In Exeter, we have access to around 75% of the world’s total human samples through the UK Biobank, the US Juvenile Diabetes Research Foundation Network for Pancreatic Organ Donors and Norway’s DiViD study. Using results from these experiments, the models will be iteratively improved. Ultimately, the aim of the project is to use the modelling environment to identify new therapeutic targets for the treatment of the disease.