Introduction
The human body is constantly subjected to an onslaught of allergens and environmental irritants. These particles can trigger immune and inflammatory responses leading to a variety of alterations in gene expression. In recent years, the study of non-coding RNAs has led to an increased understanding that gene regulation is more complex than previously imagined1,2. Among other mechanisms, small non-coding microRNAs (miRNAs) have found themselves in the role of central regulators of gene expression at the post-transcriptional level. The details of miRNA molecular function, biogenesis and processing have been thoroughly described in several reviews1-4. In canonical miRNA processing, miRNAs are transcribed by RNA polymerase II as a pri-miRNA which is then processed by the enzymes DROSHA and DCGR8 in the nucleus to form a pre-miRNA. This pre-miRNA hairpin is exported to the cytoplasm where is it cleaved by DICER into a miRNA duplex. One of the two strands is loaded into AGO2, whereas the other is degraded. It should be highlighted that miRNAs often initiate the downregulation of their target genes via imperfect binding to the 3’ untranslated regions of mRNAs. This imperfect binding leads to the suppression of multiple targets by one miRNA, while a single mRNA can be influenced by several miRNAs. There are several points to take into account when understanding miRNA nomenclature5. 1.) Novel miRNAs are named sequentially although there are exceptions for “historical” miRNAs such as let-7 and lin-4 which were first discovered in C. elegans . Currently, over 2500 miRNAs have been verified. 2.) miRNA clusters are areas where two or more miRNAs are transcribed from adjacent miRNA genes (e.g. miR17~92). 3.) miRNA strands are named -5p or -3p indicating if they originate from the 5’ or 3’ arm and either may be responsible for regulating cellular processes. Nowadays technological advances such as real-time PCR, microarray and next generation sequencing have greatly simplified the identification and validation of miRNAs, allowing for the exponential growth of investigation of miRNAs as regulatory molecules in a wide variety of research areas.
Although miRNAs were first discovered nearly thirty years ago, their detailed role in the immune system has only begun to be elucidated in the past decade. While more thoroughly studied in cancer, recent research has reported miRNA expression to be altered in skin conditions and a variety of lung diseases, including, but not limited to: idiopathic pulmonary fibrosis, cystic fibrosis, chronic obstructive pulmonary disease, and asthma6-10. The use of model systems, such as cell culture and mouse models, have furthered our knowledge of the mechanistic role of miRNAs in airway hyper-reactivity, allergy and immune responses2,4,11-13. Research into the role of miRNAs in allergy is expanding and many potential players have been identified in mouse models or in vitro studies, but their real role in human disease still remains poorly understood.
This review highlights the recent steps towards a better understanding of the role of miRNAs in allergic diseases including atopic dermatitis (AD), allergic rhinitis (AR) and asthma. Currently, sufficient evidence exists for miRNA regulation in the pathogeneses of these three allergic diseases, but, there is increasing evidence for a role of miRNAs in other allergic diseases such as food allergy or chronic rhinosinusitis4,10,13-29.Figure 1 provides an overview of miRNAs in cells and tissues that are associated with allergic diseases.