An integrated view of the epidermal environmental interface

The harsh realities of life in a terrestrial environment demand that the epidermis must respond quickly to many types of external stressors that threaten the internal milieu. We review herein how the individual protective functions of the skin (e.g., permeability barrier, antimicrobial barrier, antioxidant defense, integrity, hydration, and mechanical integrity) appear to be integrated into a broad defensive shield. Then, we will review how the epidermis responds to external perturbations through a network of extracellular signaling mechanisms and second messengers, as well as the pathophysiology of these responses in diseases such as atopic dermatitis and psoriasis. Finally, we will briefly discuss the potential therapeutic implications of this new functional paradigm.