Structure and Function of Skin Barrier: Dynamic Interaction of Langerhans Cells with Tight Junction Barrier

Skin is the structure that covers our body and protects it not only from the entry of pathogens or allergens but also from the leakage of water, solutes or nutrients. These outside-in and inside-out skin barrier functions are dependent on the epidermis, a stratified epithelial cellular sheet. Terminally differentiated cornified cellular sheets called stratum corneum (SC) constitute the outermost epidermal barrier. Beneath the SC, apical paracellular spaces of epidermal cells are sealed with tight junctions (TJs). We have recently reported in mice that Langerhans cells (LCs) elongate their dendrites to penetrate through epidermal TJs upon activation and uptake antigens from extra-TJ environment. To understand the epidermal barrier system and its deficiency observed in human skin diseases, especially in atopic dermatitis, we need to re-evaluate human epidermal barrier as a composite barrier consisting of SC and TJs and to investigate the molecular mechanism and immunological consequences of the extra-TJ antigen uptake activity of LCs.