Pathological changes in human insulitis

Purpose of review: Type 1 diabetes mellitus is a chronic disease resulting from autoimmune destruction of pancreatic β-cells in genetically predisposed individuals. The progressive loss of β-cells leads to insulin deficiency, which becomes almost invariably absolute a few years after diagnosis. The pathologic hallmark of such a disease is the mononuclear infiltration of pancreatic islets (insulitis), which has been well characterized in animal models and, to a much lesser extent in humans. Recurrent insulitis has also been shown to occur in transplanted pancreas in type 1 diabetic subjects. We here review the most recent articles that have provided novel important insights into the mechanisms involved in human islet inflammation and destruction during the immunopathogenic process leading to disease development and in recurrent autoimmunity and alloimmunity, which can result in pancreatic graft failure. Recent findings: Recent findings suggest that enteroviral infection can indeed take place in human pancreatic β-cells; however, the direct contribution of such infections to islet inflammation and destruction remains to be elucidated. On the side of molecular mechanisms of immune-mediated β-cell damage, a major role of NF-kB activity has been demonstrated. In the area of transplantation, recurrent autoimmunity with islet inflammation can take place in transplanted pancreatic tissue; however this phenomenon rarely occurs when full immunosuppression is given. Summary: Type 1 diabetes mellitus results from a chronic process of islet autoimmunity characterized by islet inflammation and destruction by several components of the immune system such as mononuclear cells, cytokine, chemokines, etc. On this background, environmental factors such as viral infections may contribute to disease development in a subset of genetically predisposed individuals