Spotlight on microRNAs in allergy and asthma

Abstract

In past 10 years, microRNAs (miRNAs) have gained scientific attention due to their importance in the pathophysiology of allergic diseases and their potential as biomarkers in liquid biopsies. They act as master post-transcriptional regulators that control most cellular processes. As one miRNA can target several mRNAs, often within the same pathway, dysregulated expression of miRNAs may alter particular cellular responses and contribute, or lead, to the development of various diseases. In this review, we give an overview of the current research on miRNAs in allergic diseases, including atopic dermatitis, allergic rhinitis, and asthma. Specifically, we discuss how individual miRNAs function in the regulation of immune responses in epithelial cells and specialized immune cells in response to different environmental factors and respiratory viruses. In addition, we review insights obtained from experiments with murine models of allergic airway and skin inflammation and offer an overview of studies focusing on miRNA discovery using profiling techniques and bioinformatic modeling of the network effect of multiple miRNAs. In conclusion, we highlight the importance of research into miRNA function in allergy and asthma to improve our knowledge of the molecular mechanisms involved in the pathogenesis of this heterogeneous group of diseases.

Keywords: allergic disease; asthma; experimental models; microRNA; pollution.

FIGURE 1

microRNA biogenesis and clinical sampling. (Left) miRNAs are transcribed in the nucleus by RNA polymerase II (RNA pol II) and processed by the enzymes Drosha and DiGeorge syndrome critical region 8 (DGCR8) from Pri‐ to Pre‐miRNA. Exportin5 acts to export Pre‐miRNAs to the cytoplasm where Dicer and the Dicer binding protein TRBP cut the hairpin to shorter duplexes. While the mature miRNA is incorporated into the miRNA induced silencing complex (miRISC) containing Ago2 and trinucleotide repeat‐containing gene 6 (TNRC6) proteins, the passenger strand is degraded. In the miRISC, the mature miRNA acts as a guide RNA for RISC proteins, of which Ago2 has the capacity to cleave mRNA if there is very high homology between the miRNA and the mRNA. If the homology is low, TNRC6 activity predominantly leads to deadenylation and degradation or translational repression of the target mRNA. In addition, miRNAs can be incorporated into different types of secretory vesicles and exit to the extracellular space. (Right) miRNAs are found in cells, tissues and fluids throughout the body. In lung diseases, miRNA levels in fluids, for example serum, plasma and urine (either protein‐bound, ie, free, or within extracellular vesicles), are often altered compared to healthy controls. This qualifies them to be used as non‐invasive biomarker for lung diseases. Other examples of clinical sampling that would allow for the identification of miRNAs in asthma, atopic dermatitis and allergic rhinitis are illustrated

FIGURE 2

Overview of miRNAs discussed in this review. miRNAs are important regulators in allergic diseases. Herein, we provide an overview of the miRNAs described within the review and the cell types or organ systems where evidence of their actions has been reported. All miRNAs have been examined in human cells unless indicated inbold italics (mouse studies) or underlined italics (human and mouse)

FIGURE 3

The effect of air pollution on miRNA networks and pathways in airway epithelial cells. Shown is a detailed schematic of miRNA action including known targets. Increased miRNA expression is indicated with upward red arrow, and decreased miRNA expression is indicated with downward blue arrow. Black arrows indicate a stimulatory effect on expression or process, and black line ending with perpendicular line indicates inhibitory effect. Smoke, pink and yellow figures represent air pollutants that may affect epithelial cells. Based on references 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118