Extracellular Vesicles and Asthma-More Than Just a Co-Existence

Abstract

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.

Keywords: airway; allergy; asthma; epigenetic(-s); exosome; extracellular vesicle (EV); inflammation; microRNA (miRNA); microvesicle (MV).

Figure 1

Basic cellular mechanisms underlying type-2 and non-type-2 asthma. For a more detailed description, please refer to the main text, Section 2. “Asthma”. AECs, airway epithelial cells; ASMC, airway smooth muscle cells; LTs, leukotrienes; ROS, reactive oxygen species; MMPs, matrix metalloproteinases; IL, interleukin; ILC, innate lymphoid cells; ILCp, ILC precursors; Th (cells), T helper (cells); IgE, immunoglobulin E; TGF-β, transforming growth factor beta; TSLP, thymic stromal lymphopoietin; CCL, C-C motif chemokine ligand; TCR, T cell receptor; APCs, antigen-presenting cells.

Figure 2

Basic processes involved in microRNA (miRNA) biogenesis and function. For detailed description, please refer to the main text, Section 4. “MicroRNA”. RISC, RNA-induced silencing complex; mRNA, messenger RNA.

Figure 3

Extracellular vesicle- (EV-) mediated communication between cells crucial for asthma pathobiology. If not otherwise stated, EVs are thought to carry their usual content such as microRNAs, proteins, lipids, etc. For a more detailed description, please refer to the main text, Section 5.1 “Airway Epithelial Cells and Fibroblasts”, Section 5.2 “Antigen-Presenting Cells”, Section 5.3 “Granulocytes and Mast Cells”, and Section 5.4 “Platelets”. SOCS3, suppressor of cytokine signaling 3; TF, tissue factor; EMT, epithelial-mesenchymal transition; INPP4A, inositol polyphosphate 4-phosphatase type I A; OX40L, OX40 ligand; MDSCs, myeloid-derived suppressor cells; otherwise, please, refer to the legend to Figure 1.