Abstract
Skin barrier function relies on three essential components: stratum corneum (SC) lipids, natural moisturizing factors (NMFs), and the acidic pH of the SC surface. Three endogenous pathways contribute to acidity: free fatty acids from phospholipids, trans-urocanic acid from filaggrin (FLG), and the sodium-proton antiporter (NHE1) activity. An acidic SC environment boosts the activity of enzymes to produce ceramides, which are vital for skin health. Conversely, an elevated pH can lead to increased skin infections, reduced lipid-processing enzyme activity, impaired permeability barrier recovery, and compromised integrity and cohesion of the SC due to increased serine protease (SP) activity. Elevated SC pH is observed in neonatal, aged, and inflamed skin. In atopic dermatitis (AD), it results from decreased NMF due to reduced FLG degradation, decreased fatty acids from reduced lamellar body secretion, and reduced lactic acid due to decreased sweating. Moreover, the imbalance between SP and SP inhibitors disrupts barrier homeostasis. However, acidifying the SC can help restore balance and reduce SP activity. Acidic water bathing has been found to be safe and effective for AD. In three different AD murine models, SC acidification prevented the progression of AD to respiratory allergies. In aging skin, a decrease in NHE1 leads to an increased skin pH. Mild acidic skin care products or moisturizers containing NHE1 activators can normalize skin pH and improve barrier function. In conclusion, maintaining the acidity of the SC is crucial for healthy skin barrier function, leading to significant benefits for various skin conditions, such as AD and aging-related skin issues.