The impact of microRNAs on alterations of gene regulatory networks in allergic diseases

Abstract

Allergic diseases including asthma are worldwide on the rise and contribute significantly to health expenditures. Allergic diseases are prototypic diseases with a strong gene by environment interaction component and epigenetic mechanisms might mediate the effects of the environment on the disease phenotype. MicroRNAs, small non-coding RNAs (miRNAs), regulate gene expression post-transcriptionally. Functional single-stranded miRNAs are generated in multiple steps of enzymatic processing from their precursors and mature miRNAs are included into the RNA-induced silencing complex (RISC). They imperfectly base-pair with the 3'UTR region of targeted genes leading to translational repression or mRNA decay. The cellular context and microenvironment as well the isoform of the mRNA control the dynamics and complexity of the regulatory circuits induced by miRNAs that regulate cell fate decisions and function. MiR-21, miR-146a/b and miR-155 are among the best understood miRNAs of the immune system and implicated in different diseases including allergic diseases. MiRNAs are implicated in the induction of the allergy reinforcing the Th2 phenotype (miR-19a, miR-24, miR-27), while other miRNAs promote regulatory T cells associated with allergen tolerance or unresponsiveness. In the current chapter we describe in detail the biogenesis and regulatory function of miRNAs and summarize current knowledge on miRNAs in allergic diseases and allergy relevant cell fate decisions focusing mainly on immune cells. Furthermore, we evoke the principles of regulatory loops and feedback mechanisms involving miRNAs on examples with relevance for allergic diseases. Finally, we show the potential of miRNAs and exosomes containing miRNAs present in several biological fluids that can be exploited with non-invasive procedures for diagnostic and potentially therapeutic purposes.

Keywords: Asthma; DICER; Epigenetics; Exosome; Food allergy; IgE; Inflammation; Network motifs; Post-transcriptional gene regulation; RISC complex; Regulatory T cells (tregs); Th2; miRNA.