NF-κB in Type 1 Diabetes

Yuxing      Zhao; Balasubramanian      Krishnamurthy; Zia      U.A. Mollah; Thomas      W.H. Kay; Helen      E. Thomas

Abstract

Type 1 diabetes is an autoimmune disease in which pancreatic beta cells are destroyed by autoreactive T cells. It is a common pediatric disease with increasing incidence. Islet transplantation may be a therapeutic option, however, the current limitations of this procedure mean that for most sufferers of type 1 diabetes there is no cure. The transcription factor NF-κB has been widely studied for its role in development of type 1 diabetes. Recent data have shown that NF-κB is required for activation of autoreactive T cells, and its hyperactivity in monocytes and dendritic cells results in altered cytokine secretion and antigen presentation, which ultimately contributes to the initiation of type 1 diabetes. NF-κB is also activated by a number of proinflammatory cytokines to regulate both the survival and death of beta cells. The critical role of NF-κB in type 1 diabetes renders it a promising pharmaceutical target in the intervention of this disease and further understanding of the NF- κB pathway will have an important implication on the development of novel and safe therapeutic strategies.

Keywords: Type 1 diabetes, NF-κB, pancreatic beta cells, cytokine secretion, Islet transplantation, beta-cell destruction, insulitis, p65/RelA, RelB, p100/NF-B1, p105/NF-B2