The role of tight junctions in skin barrier function and dermal absorption

The skin protects our body from external assaults like pathogens, xenobiotics or UV irradiation. In addition, it prevents the loss of water and solutes. To fulfill these important tasks, a complex barrier system has developed which comprises the stratum corneum, tight junctions, the microbiome, the chemical barrier and the immunological barrier. These barriers do not act separately, but influence each other e.g. after external manipulation or in skin diseases. Especially the two mechanical barriers, i.e. stratum corneum and tight junctions, are of great interest for drug delivery, because they are the first interaction partners of drug delivery systems and play the major role in skin absorption. Tight junctions are of special interest, as they are centrally localized in this complex barrier system in the outermost viable layer - the stratum granulosum of the interfollicular epidermis and the companion cell layer of the hair follicle - and because they can react very quickly to stimuli. We summarize here our current knowledge about tight junction barrier function in mammalian interfollicular epidermis and hair follicles, and the interaction of tight junctions with other skin barrier components in health and disease. Furthermore, we discuss their relevance for drug delivery and provide examples for tight junction modulators.