β-Cells, Autoimmunity, and the Innate Immune System: “un Ménage á Trois”?

Abstract

Type 1 diabetes is generally believed to result from an autoimmune attack selectively destroying β-cells in the pancreatic islets of Langerhans. Indeed, with the recent discovery of cytotoxic T cells specifically recognizing β-cells infiltrating insulitic lesions in the pancreas, the ultimate proof of an autoimmune nature in human type 1 diabetes seems to be framed (1). This could imply that one of the last pieces of the puzzle of the pathogenesis of type 1 diabetes has been laid. But is this all there is to it? In this issue of Diabetes , Valle et al. (2) present their perhaps surprising observation that slightly reduced circulating neutrophil counts associate with type 1 diabetes. The authors demonstrate that this phenomenon is not necessarily a consequence of impaired glycemic control because similarly reduced frequencies of neutrophils could also be found in nondiabetic first-degree relatives of type 1 diabetic patients with increased risk to disease but with normoglycemia, whereas type 2 diabetic patients showed neutrophils in the blood at normal counts. In contrast, the authors could demonstrate mild neutrophil infiltrates in exocrine pancreas tissue in some type 1 diabetic organ donors …