The Skin Barrier as an Integrated System: Physical, Chemical, Microbial, and Immunological Components and Their Key Interactions

The skin barrier is a dynamic and multicomponent system that serves as the first line of protection for the body against pathogens, allergens, and transepidermal water loss. This narrative review, based on key insights from an international meeting on skin barrier function, provides a summary of the structural, chemical, microbial, and immunological components that form the skin barrier. The interplay between physical and chemical architecture of the stratum corneum in regulating barrier permeability and balancing immune responses is also discussed, particularly the roles of the acid mantle and ceramides in the extracellular lipid matrix. The interactions between the exposome, the skin and gut microbiomes, and the genome that influence skin barrier function are also considered. Finally, we review developmental and ethnic differences in skin barrier properties, which underscore the need for personalized approaches to skin care and disease management. Overall, the topics discussed in this narrative review highlight the importance of maintaining skin barrier integrity as a cornerstone of skin health, and present recent advances in our understanding of the complex interactions among skin barrier components, immune cells, and environmental factors. However, further research using innovative tools, such as the skin interactome, is essential for advancing targeted therapies and patient-centered care.