Regulation of mast cell activation by extracellular vesicles in cow’s milk casein-induced allergic responses

Background: Food allergy is a hypersensitive immune reaction to food proteins including cow’s milk protein. Extracellular vesicles (EVs), such as exosomes, are newly discovered intercellular conveyors of functional molecular mechanisms and mediated intercellular interactions involving mast cells and are particularly relevant to allergy. Objective: In this study, we investigated whether cow’s milk casein-induced allergy (CIA)-derived EVs can modulate mast cell activation. Results: EVs in CIA mice and control mice were isolated using the ultracentrifugation method and the isolated EVs were quantified using BCA analysis. CIA responses were determined through changes in body temperature and systemic symptom score. The number of EVs was higher in CIA-derived EVs compared to normal EVs. EVs marker proteins such as CD63 and CD9 were elevated in CIA-derived EVs. The levels of EV-associated cytokines such as IL-6, IL-8, and TNF-α were significantly elevated in CIA-derived EVs. In addition, CIA-derived EVs significantly induced degranulation via Lyn kinase activation in mouse bone marrow-derived mast cells and human mast cells. Conclusion: Our results demonstrate that CIA-derived EVs can induce a reaction similar to cow’s milk allergic reaction via mast cell activation. These results provide an insight into the pathology of cow’s milk allergy and a potential therapeutic approach through targeting EV release and/or uptake.