Nasal Epithelial Extracellular Vesicles Correlate with Type 2 Inflammation During Aspirin-induced Respiratory Reactions

Abstract

Extracellular vesicles (EVs) are membrane-bound particles secreted by cells with emerging roles in intercellular communication during tissue homeostasis and disease. Although EVs are abundant in respiratory biofluids, their cellular sources, critical cargos, and functions in the airway remain poorly understood. To determine how EV populations are changed in respiratory fluids during a chronic tissue inflammatory response, nasal EVs were assayed in 23 control participants and 22 participants with Aspirin-Exacerbated Respiratory Disease (AERD). Nasal lining fluid from participants was found to contain abundant EVs by electron microscopy and tunable resistive pulse sensing. Subset-specific EV subpopulations defined by the monocyte/macrophage marker CD14 or the epithelial marker CD133/1 were increased in participants with AERD. To test how EVs change during an acute exacerbation, nasal lining fluid EVs were assessed in participants with AERD who were repeatedly sampled during an aspirin-induced respiratory reaction. The abundance of several EV subpopulations dynamically correlated with levels of cysteinyl leukotrienes and tryptase in AERD nasal lining fluid. Together, these data implicate EVs in a dynamic signaling network that drives tissue inflammation during aspirin-induced type 2 immune activation in AERD.

Keywords: Aspirin-exacerbated respiratory disease; Epithelium; Extracellular vesicles; Leukotrienes; Macrophages.