- IL-13 acts directly on keratinocytes to:
- Reduce expression of skin barrier proteins and lipids, thereby further disrupting the skin barrier2-4
- Down-regulate the expression of antimicrobial peptides, and thereby play a role in the dysbiosis of the skin, which is typically characterized by a strong colonization with Staphylococcus aureus and an increased risk of secondary skin infections5
- Stimulate the secretion of chemokines and cytokines, which attracts more immune cells and amplifies the inflammatory response6
- IL-13 may stimulate peripheral itch-sensory neurons, activating itch signaling and scratching7
- IL-13 down-regulates MMP-13 expression in human dermal fibroblasts and may thereby decrease collagen degradation, resulting in fibrosis with excess collagen deposition, as found in the thickened dermis of chronic lichenified AD skin lesions8
- Chronic itch sensations and associated scratching are components of a dynamic pathological process known as the itch-scratch cycle9
- Scratching exacerbates itch sensation through damage to the skin barrier, increasing exposure to allergens and microbes that may further amplify the inflammation
- The epithelial stress response also releases cytokines that activate immune cells to promote inflammation
- The released cytokines further stimulate peripheral itch-sensory neurons, resulting in itch signaling and further scratching