MicroRNAs as new tools for exploring type 1 diabetes: Relevance for immunomodulation and transplantation therapy

Abstract

Type 1 diabetes (T1D) is a polygenic disorder where loci within the human leukocyte antigen (HLA) account for most of the genetic susceptibility. Nongenetic factors, most likely environmental, are also involved in the pathogenesis of the disease, resulting in T-cell-mediated autoimmune attack against pancreatic beta cells. Although our understanding of the natural history of T1D has significantly improved during the last decades, the pathogenesis of the disease remains elusive as are successful strategies for primary intervention. Interesting findings are expected from the emerging field of microRNAs (miRNAs), a family of endogenous small noncoding RNA molecules that regulate gene expression. They play a key role in post-transcriptional regulation by selectively binding complementary messenger RNAs, thus affecting translation. miRNAs affect key biological processes including cell proliferation, differentiation, development, and metabolism. In addition, miRNAs are also involved in the regulation of the immune system and insulin secretion. Interestingly, miRNAs have been identified in both normal and pathological conditions, functioning as predictive markers in certain human diseases. Herein, we have discussed the potential application of this new field to T1D. Research in this area may help to identify variations in genes coding for selected miRNAs that may contribute to diabetes susceptibility. In addition, mechanistic studies on the role of miRNAs in the modulation of the immune system may elucidate important regulatory mechanisms, identifing potential therapeutic targets to ameliorate responses to islet tranplantation. © 2011 by Elsevier Inc. All rights reserved.