Type 1 diabetes (T1D) is a pancreatic disease marked by the autoimmune destruction of insulin–secreting beta cells within the endocrine compartment, leading to chronic hyperglycemia and long–term complications. Despite extensive studies into the autoimmunity that targets beta cells, a complete understanding of the pathogenesis of T1D remains unclear. A recent study by Fasolino et al. demonstrated that the exocrine ductal cells in T1D donors, compared to non–diseased control donors, have an elevated expression of a MHC class II molecule, HLA–DR. MHC class II molecules are known to be expressed by antigen presenting cells (APCs) that process and present extracellular antigens to CD4–expressing T helper cells. Fasolino et al. also found that CD4+ T cells, compared to CD8+ T effector cells, are located more frequently in the neighborhood of HLA–DR expressing ductal cells. These results raised the intriguing possibility that pancreatic ductal cells may function as APCs. In this study, we propose to conduct a more comprehensive assessment of proteins involved in antigen processing and presentation in pancreatic ductal cells of T1D donor tissues, compared to control non–diseased donor tissues, using co–immunofluorescence staining technique. Our proposed studies, if successful, will contribute to a new line of research addressing the cross talk between exocrine and endocrine pancreas in the pathogenesis of T1D, which may lead to new therapeutic targets for T1D.
