Advances and Highlights of miRNAs in Asthma: Biomarkers for Diagnosis and Treatment

Abstract

Asthma is a heterogeneous inflammatory disease of the airways that causes breathing difficulties, episodes of cough and wheezing, and in more severe cases can greatly diminish quality of life. Epigenetic regulation, including post-transcriptional mediation of microRNAs (miRNAs), is one of the mechanisms behind the development of the range of asthma phenotypes and endotypes. As in every other immune-mediated disease, miRNAs regulate the behavior of cells that shape the airway structure as well as those in charge of the defense mechanisms in the bronchi and lungs, controlling cell survival, growth, proliferation, and the ability of cells to synthesize and secrete chemokines and immune mediators. More importantly, miRNAs are molecules with chemical and biological properties that make them appropriate biomarkers for disease, enabling stratification of patients for optimal drug selection and thereby simplifying clinical management and reducing both the economic burden and need for critical care associated with the disease. In this review, we summarize the roles of miRNAs in asthma and describe how they regulate the mechanisms of the disease. We further describe the current state of miRNAs as biomarkers for asthma phenotyping, endotyping, and treatment selection.

Keywords: asthma; biomarkers; endotyping; epigenetics; miRNAs; phenotyping; treatment.

Figure 1

Role of miRNAs through the diverse pathophysiological mechanisms of asthma disease. miRNAs are able to regulate the functions of the airway structural cells, starting with bronchial epithelial cells, where miRNAs control remodeling, repair, and cytokine synthesis, and continuing with the smooth muscle compartment, as there are reports of miRNAs regulating contraction, hyperactivity, remodeling, and cytokine production. T cells (both Th1 and Th2) are also targets for miRNA-modulation in asthma, especially regarding polarization of immune responses toward the T2 axis. The behavior of eosinophils, the main effectors of severe asthma, is also regulated by miRNAs, altering their tissue infiltration capacity; meanwhile, other miRNAs control basophil degranulation and cytokine release. Finally, miRNAs are capable of tuning the actions of macrophages and dendritic cells, modulating their cytokine production above all.

Figure 2

miRNAs are involved in virally induced asthma exacerbations. Several studies have shown the role of miRNAs in different mechanisms of viral exacerbations in asthma, most of which have sought to unravel how miRNAs control responses against the specific virus or how the virus interacts with host cells. Findings from this research reveal that miRNAs modulate antiviral immune responses, control virus replication, and determine how immune cytokine responses are orchestrated or regulated against respiratory viruses including human rhinovirus (hRV), influenza virus (IV), human metapneumovirus (hMPV), human coronavirus (hCoV), and respiratory syncytial virus (RSV). Sharp arrows indicate relationship or causation while blunt arrows signal inhibition.