Attacking the source: anti-PDX-1 responses in type 1 diabetes.

Type 1 diabetes (T1D) develops as a consequence of abnormal responses against several self-antigens, eventually leading to the autoimmune attack and destruction of the insulin-producing beta cells in the pancreas. In this issue of Laboratory Investigation, Li et al propose the transcription factor Pancreatic and duodenal homeobox 1 (PDX-1) as a T1D autoantigen by demonstrating autoreactivity to this pancreas-specific protein in both the NOD mouse model and patients with T1D. Because of the known roles of PDX-1 in pancreatic development as well as beta cell maintenance and function, targeting of PDX-1 expressing cells may result in the elimination of not only beta cells but also the progenitor cells required for regeneration of insulin-producing cells.