Immune cell trafficking to the islets during type 1 diabetes

Summary Inhibition of immune cell trafficking to the pancreatic islets during type 1 diabetes (T1D) has therapeutic potential, since targeting of T cell and B cell trafficking has been clinically effective in other autoimmune diseases. Trafficking to the islets is characterized by redundancy in adhesion molecule and chemokine usage, which has not enabled effective targeting to date. Additionally, cognate antigen is not consistently required for T cell entry into the islets throughout the progression of disease. However, myeloid cells are required to enable T cell and B cell entry into the islets, and may serve as a convergence point in the pathways controlling this process. In this review we describe current knowledge of the factors that mediate immune cell trafficking to pancreatic islets during T1D progression. Immune cell migration to the pancreatic islets during type 1 diabetes occurs by transendothelial migration, through a series of steps including rolling, arrest, and crawling on the vascular wall culminating with diapedesis through the endothelial barrier. Migration to the islets is characterized by redundancy in adhesion molecule and chemokine usage, and variable requirement for cognate antigen. However, myeloid cells are required to enable T cell and B cell entry into the islets and may serve as a convergence point in the pathways controlling this process.