Extracellular vesicles in lung microenvironment and pathogenesis

Increasing attention is being paid to the role of extracellular vesicles (EVs) in various lung diseases. EVs are released by a variety of cells, including respiratory cells and immune cells, and they encapsulate various molecules, such as proteins and microRNAs, as modulators of intercellular communication. Cancer cell-derived EVs play crucial roles in promoting tumor progression and modifying their microenvironment. By contrast, noncancerous cell-derived EVs demonstrate protective functions against injury, such as tissue recovery and repair, to maintain physiological homeostasis. Airway cells in contact with harmful substances may alter their EV composition and modify the balanced reciprocal interactions with surrounding mesenchymal cells.

• Extracellular vesicles (EVs) maintain lung physiological homeostasis.
• Various triggers can modify EV components and enhance EV secretion in the airway.
• EVs play important roles in inflammatory airway disease and in lung cancer pathogenesis.
• Mesenchymal stem cell-derived EVs may have therapeutic potential in lung damage.

Extracellular vesicle (EV) function in normal and stressed airway physiology. (A) A broad range of respiratory cell types can release EVs. In the air space, alveolar macrophage-derived EVs can control cellular homeostasis and differentiation by miR-223 transfer and also control the inflammatory signaling by SOCS (suppressor of cytokine signaling) protein transfer to lung epithelial cells. Lung epithelial cell-derived EVs may regulate the finely balanced reciprocal interaction of the epithelial–mesenchymal trophic unit (EMTU). Lung endothelial cell-derived EVs secrete into the blood. (B) In stressed airway physiology, exposure to various stress triggers, such as infection, cigarette smoke, DNA damage, and oxidative stress, can modify EV composition and enhance EV secretion, thus leading to changes in the surrounding microenvironment. EVs derived from injured mammalian cells (particularly macrophages) have a variety of proinflammatory effects, which result in improved innate immunity efficacy.