Figure 2. Mechanisms of skin barrier dysfunction in atopic dermatitis resulting in food allergy.
Environmental pollutants, detergents, microbial dysbiosis and genetics such as FLG loss of function mutations can lead to disruptions to the epithelial barrier. Skin barrier impairment leads to skin inflammation resulting in atopic dermatitis. Epicutaneous exposure to food allergens in the context of an impaired barrier may trigger food allergen sensitization through Th2-dependent pathways: Specific resident dendritic cell (DC) subsets capture allergens in the skin and transport them to skin-draining lymph nodes where they are presented to CLA+ skin homing T cells. IL‐4 and IL‐13 cytokines promote B‐cell isotype switching to specific IgE (sIgE), and upon differentiating into plasma cells, yield allergen‐specific IgE antibodies. The sIgE bind to high‐affinity FcεRI receptors on the surface of mast cells and basophils. During the sensitization process, a memory pool of allergen‐specific B cells and T helper 2 cells are produced. Upon subsequent oral antigen exposure (consumption of the allergenic food), cross-linking of sIgE on the FcεRI receptors trigger mast cell degranulation, release of histamine and other inflammatory mediators, culminating in the clinical allergic response. The presence of S. aureus enhances pro-inflammatory responses which heighten risk of food allergy development. S. aureus colonization, such as bymethicillin-resistant S. aureus (MRSA), and exposure to staphylococcal enterotoxin B (SEB), has been shown to increase risk of food allergy (FA) independent of AD severity. S. aureus abundance was also found to be positively correlated with transepidermal water loss (TEWL) in patients with AD and FA. (Created with BioRender.com)