Type 1 diabetes - an auto-inflammatory disease: a new concept, new therapeutical strategies

Abstract

Type 1 diabetes (T1D) is characterized by a progressive destruction of pancreatic beta-cells that results in absolute insulin deficiency and the need for daily insulin treatment. However, the auto-inflammatory nature of the disease has been recently demonstrated by understanding the precise cellular/molecular mechanisms of type 1 diabetes’ aetiology and progression. Studies in NOD mice have shown that the disease occurs as consequence of a breakdown in the immune-system balance. Although the detection of islet specific auto antibodies in sera from humans with T1D was the first sign of an autoimmune disease, there is strong evidence in both, mice and humans that auto-reactive T cells play a prominent role in disease onset and progression. Destruction of beta-cells is mainly due to the secretion of powerful pro-inflammatory cytokines, such as Interleukine -1 beta (IL-1b), tumor-necrosis-factor alpha (TNFα) and interferon gamma(IFNγ). Recent studies have shown that Foxp3 regulatory T cells’ (Treg) activity is diminished, which affects the fine balance of the peripheral self-tolerance and immune activation.