Thymus and type 1 diabetes: an update

Abstract

Type 1 diabetes (T1D) is a chronic disease resulting from the selective autoimmune destruction of pancreatic islet β cells. The absence and/or breakdown of immune self-tolerance to islet β cells is now recognized as the essential cause for the development of the diabetogenic autoimmune response. For a long time, a failure in peripheral tolerogenic mechanisms was regarded as the main source of an inappropriate immune process directed against insulin-secreting β cells. While defective peripheral self-tolerance still deserves to be further investigated, the demonstration that all members of the insulin gene family are transcribed in thymic epithelial cells (TECs) of different species under the control of the AutoImmune REgulator (AIRE) gene/protein has highlighted the importance of central self-tolerance to insulin-secreting islet β cells. Moreover, there is now evidence that a primary or acquired failure in thymus-dependent central self-tolerance to β cells plays a primary role in T1D pathogenesis. This novel knowledge is currently translated into the development of innovative tolerogenic/regulatory approaches designed to reprogram the specific immune self-tolerance to islet β cells.