Abstract
Asthma is a chronic inflammatory disease of the airway diagnosed with different endotypes and phenotypes, characterized by airway obstruction in response to allergens, bacterial/viral infections, or pollutants. Several cell types such as the airway epithelial cells, mesenchymal stem cells and different immune cells including dendritic cells (DCs), T and B cells and mast cells play an essential role during the pathobiology of asthma. Extracellular vesicles (EVs) are membranous nanovesicles produced by every cell type that facilitates intercellular communications. EVs contain heterogeneous cargos that primarily depend on the composition or cell type of origin and they can alter the physiological state of the target cells. EVs encompass a wide variety of proteins including Tetraspanins, MHC classes I and II, co-stimulatory molecules, nucleic acids such as RNA, miRNA, piRNA, circRNA, and lipids like ceramides and sphingolipids. Recent literature indicates that EVs play a pivotal role in the pathophysiology of allergic asthma and may potentially be used as a novel biomarker to determine endotypes and phenotypes in severe asthmatics. Based on the prior reports, we speculate that regulation of EVs biogenesis and release might be under the control of circadian rhythms. Thus, circadian rhythms may influence the composition of the EVs, which alter the microenvironment that results in the induction of an immune-inflammatory response to various environmental insults or allergens such as air pollutants, ozone, diesel exhaust particles, pollens, outdoor molds, environmental tobacco smoke, etc. In this mini-review, we summarize the recent updates on the novel role of EVs in the pathogenesis of asthma, and highlight the link between circadian rhythms and EVs that may be important to identify molecular mechanisms to target during the pathogenesis of chronic inflammatory lung disease such as asthma.
Highlights
Asthma is a chronic airway disorder and generally characterized by various symptoms like bronchial hyperreactivity, airway obstruction and inflammation-induced airway remodeling
These studies implicate that allergic airway inflammation and immune response during asthma can be reduced or exaggerated depending on the miRNA cargo present in dendritic cells (DCs)-derived exosomes
Extracellular vesicles (EVs) have demonstrated their prime role in causing augmented immune-inflammatory response and airway remodeling during asthma
Summary
Asthma is a chronic airway disorder and generally characterized by various symptoms like bronchial hyperreactivity, airway obstruction and inflammation-induced airway remodeling. Dendritic cells can inhibit the differentiation of Th1 and promote Th2 through the STAT3 pathway by secreting exosomes packed with miR-21[15,62,63] [Table 1 and Figure 1] These studies implicate that allergic airway inflammation and immune response during asthma can be reduced or exaggerated depending on the miRNA cargo present in DC-derived exosomes. This emphasizes the need for extensive research that will thoroughly isolate and characterize EVs from specific subsets of dendritic cells to understand the mechanism by which allergens dictate the immune response differentially among individuals in a population This will help in the clinical diagnosis of the endotypes or phenotypes of asthma and direct patients with better alternative therapies, especially among severe asthmatics. Future research will hold accountable to find the missing link and direct role of EVs in circadian rhythms and asthma pathophysiology using novel in vitro and in vivo approaches
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