MicroRNAs: A Link Between Type 1 Diabetes and the Environment?

Abstract

Type 1 diabetes (T1D ) is an autoimmune disease characterized by selective destruction of insulin-producing pancreatic β-cells. Although T1D is known to be largely immunological, increasing evidence suggests the importance of genetic and environmental factors, although the relative importance of these components is yet to be fully elucidated. There is a substantial body of evidence to support a major role for viruses in the initiation of islet autoimmunity and/or acceleration to clinical T1D. In particular, epidemiological data as well as substantial data obtained through animal models, cell lines and human studies support a role for enterovirus (EV) infections. EV infections are more frequent in newly diagnosed T1D patients compared to healthy controls, EV-RNA and protein have been detected in intestine, blood and pancreatic biopsies of patients with T1D. EVs contribute to β-cell damage by multiple mechanisms, such as direct cytolysis of infected β-cells, islet inflammation, and molecular mimicry. MicroRNAs (miRNAs) are endogenous small non-coding RNAs molecules that regulate gene expression through translational repression or gene silencing. They affect cell growth, proliferation, differentiation, development, apoptosis and maintenance of tissue identity. They are implicated in immune system regulation and autoimmune destruction of pancreatic β-cells. The relationship between EVs infections, miRNAs, and development of T1D is discussed aiming to describe genes encoding miRNA signatures that may be involved in T1D. Many miRNAs, and potentially other small regulatory RNA molecules discussed through this chapter, are involved in immune regulation and modulation, which may provide novel diagnostic, prognostic and therapeutic alternatives for Type 1 diabetes (T1D) in future.