Dendritic Cell-Derived Extracellular Vesicles Mediate Inflammation in Egg-Allergy Patients

Atopic allergy is rising globally and placing a significant strain on healthcare systems, yet the understanding of the underpinning mechanisms of allergic sensitisation remains incomplete. Extracellular vesicles (EVs) have recently emerged as important mediators of immune modulation due to their diverse cargo and therefore may play a mechanistic role in allergic sensitisation development. Thus, this study investigated whether EVs released by activated dendritic cells (DCs) contribute to allergic sensitisation of the common egg allergen, ovalbumin (OVA). DCs were generated from human monocytes cultured with GM-CSF and IL-4, then stimulated with LPS and/or OVA. EVs were subsequently isolated using size-exclusion chromatography and added to freshly isolated naïve T cells at defined time points. T-cell responses were then analysed using spectral flow cytometry. The results highlight EVs derived from LPS or LPS+OVA-stimulated DCs enhanced IL-4 production and reduced IFN-γ production in naïve T cells from egg-allergic donors, indicating a shift toward a Th2 profile. In healthy donors, LPS-induced DC EVs also suppressed IFN-γ expression. Notably, EVs alone were insufficient to activate T cells without CD3/CD28 co-stimulation, suggesting that EVs may function as a “third signal” shaping T-cell polarisation. These findings highlight a potential role for DC-derived EVs in initiating allergic sensitisation.