The Role of Extracellular Vesicles in Atopic Dermatitis

Abstract

Atopic dermatitis, or eczema, is the most common chronic skin disorder, characterized by red and pruritic lesions. Its etiology is multifaceted, involving an interplay of factors, such as the allergic immune response, skin barrier dysfunction, and dysbiosis of the skin microbiota. Recent studies have explored the role of extracellular vesicles (EVs), which are lipid bilayer-delimitated particles released by all cells, in atopic dermatitis. Examination of the available literature identified that most studies investigated EVs released by Staphylococcus aureus, which were found to impact the skin barrier and promote the release of cytokines that contribute to atopic dermatitis development. In addition, EVs released by the skin fungus, Malassezia sympodialis, were found to contain allergens, suggesting a potential contribution to allergic sensitization via the skin. The final major finding was the role of EVs released by mast cells, which were capable of activating various immune cells and attenuating the allergic response. While research in this area is still in its infancy, the studies examined in this review provide encouraging insights into how EVs released from a variety of cells play a role in both contributing to and protecting against atopic dermatitis.

Keywords: Malassezia sympodialis; Staphylococcus aureus; allergic sensitization; atopic dermatitis; extracellular vesicles; mast cells.

Figure 1

Immunopathology of AD: a comparison of healthy and lesional skin. S. aureus and Malassezia are present on healthy skin but overabundant on lesional skin. The damaged skin barrier facilitates their entry. They act as allergens on AD skin, triggering the allergic response through their presentation by dendritic cells to T cells. These differentiate into T helper 2 cells and secrete IL-4 and IL-13 cytokines, which induce the secretion of IgE by B cells and also promote M2 macrophage differentiation. This IgE binds to receptors on mast cells and causes degranulation, which is the release of mediators like histamine. These activate sensory nerves, causing itchiness. Scratching follows, which further damages the skin barrier, perpetuating the cycle. Created using BioRender.

Figure 2

Summary of cells of origin, characteristics, and effects of S. aureus-, M. sympodialis-, and mast cell-derived EVs. SEVs decrease keratinocyte viability and increase antibiotic resistance, epidermal thickening, and the release of pro-inflammatory cytokines. The direction of effect seems to be towards a promotion of AD pathogenesis. Similarly, MalaEx increase allergen dissemination, skin barrier degradation, and the release of pro-inflammatory cytokines. However, by increasing lymphocyte activation, dendritic cell maturation, and Th2 differentiation while decreasing free IgE, MCEVs seem to have a protective tendency in AD. Created using BioRender.