The skin barrier as an innate immune element

Since life in a terrestrial environment threatens mammals continuously with desiccation, the structural, cellular, biochemical, and regulatory mechanisms that sustain permeability barrier homeostasis have justifiably comprised a major thrust of prior and recent research on epidermal barrier function. Yet, the epidermis mediates a broad set of protective 'barrier' functions that includes defense against pathogen challenges. Permeability and antimicrobial function are both co-regulated and interdependent, overlapping through the dual activities of their lipid/protein constituents. Most of the defensive (barrier) functions of the epidermis localize to the stratum corneum (SC), which limits pathogen colonization through its low water content, acidic pH, resident (normal) microflora, and surface-deposited antimicrobial lipids (1 degree free fatty acid). These various barrier functions are largely mediated by either the corneocyte or the extracellular matrix, and it is both the localization and the organization of secreted hydrophobic lipids into characteristic lamellar bilayers that is critical not only for permeability barrier function, but also for antimicrobial function through its contribution to the maintenance of SC integrity. Low constitutive levels of antimicrobial peptides under basal conditions emphasize the key role of epithelial structure in antimicrobial defense. But antimicrobial peptide synthesis and delivery to the SC interstices accelerates after external insults to the barrier.