Massimo Pietropaolo, MD
Type 1 diabetes (T1D) is an autoimmune disorder caused by the maturation and activation of autoreactive T cells that recognize autoantigens of pancreatic β cells. These activated autoreactive T cells migrate to the β cells within Langerhans’ islets of the pancreas and specifically attack and destroy insulin production by these cells. In normal individuals, such autoreactive T cells are selected against during maturation in the thymus. This process, termed negative selection, occurs in the lower medullary region of the thymus, where medullary thymic epithelial cells (mTECs) present tissue-specific self peptides to the developing T cell repertoire. Those cells that recognize self peptides activate a transcription factor called Autoimmune Regulator of Expression (AIRE), which is a 54.5-kDa protein that is expressed by mTECs and regulates tissue-specific deletion of autoreactive T cells. The goal of our research is to determine the importance of AIRE in regulating negative selection during the development of autoreactive T cells in non-obese diabetic (NOD) mice, as well as if AIRE expression recovery can alleviate the autoimmune response.