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.