Co-Regulation of Epidermal Permeability Barrier Function and Immune Function: A Narrative Review

The epidermal permeability barrier, primarily located in the stratum corneum, is largely determined by keratinocyte function in the epidermis. Various internal and external factors can directly or indirectly influence keratinocyte function, leading to changes in epidermal permeability barrier function. Among internal factors, cytokines and immune cells can both positively and negatively regulate this barrier. Conversely, epidermal permeability barrier function also influences cytokine expression and immune cell activity. Studies show that increased interleukin (IL)-1α expression or topical application of IL-6 and tumor necrosis factor-α accelerates epidermal permeability barrier repair in acutely disrupted skin. Additionally, mast cells and Toll-like receptor 2 are essential for the formation of the epidermal permeability barrier. However, IL-4, IL-22, and histamine impair its function. Disruption of the epidermal permeability barrier further amplifies cytokine expression, T-cell maturation, and inflammatory cell infiltration in the skin. Thus, epidermal permeability barrier function and immune function co-regulate each other, with proper management of one benefiting the other. This review briefly summarizes the evidence for this co-regulation and its clinical significance.