Despite its aesthetically pleasing appendages such as the hairand nails, its pliable nature, its flexibility, and its responsiveness,the skin is a master in the art of self-defense — provingthat a tissue need not be hard in order to be tough. In additionto serving as the body’s outermost protective covering,the skin barrier integrates the body’s physiology withthe terrestrial environment. The epidermal barrier works in2 ways: as an inside-out barrier, to minimize transepidermalwater loss, and as an outside-in barrier, as a sentry to preventinvasion by infectious agents and noxious substances (1-5).
In addition to the 2 major structural layers of the skin, theepidermis and the dermis, the skin is also home to a numberof other cell types and structures that each play a unique rolein its function (6). There are resident dendritic cells, knownas Langerhans cells, which are the antigen-presenting cellsof the skin interspersed among the keratinocytes that providethe first line of defense against invasion. Mast cells residein the dermis, and their degranulation releases vasoactive aminesand other proinflammatory mediators that induce immediate hypersensitivityresponses such as urticaria (7).
The skin is also populated by eccrine (sweat) glands, whichallow for temperature regulation via sympathetic nervous systemcontrol of an intricate network of lymphatic and blood capillariesthat reside in the dermis, as well as the apocrine (scent) glands,which are believed to emit secretions and pheromones for sexualcommunication (8). The sebaceous gland is attached to the hairfollicle and secretes sebum to the skin surface that keeps itsupple and waterproof (9). The hair follicle, in addition togenerating the hair shaft, also provides a protective nicheto several stem cell populations in the skin, including thekeratinocyte stem cell, the melanocyte stem cell, a populationof epidermal neural crest stem cells, and the dermal stem cellcompartment, known as the dermal papilla (10-13). There areseveral contractile cell populations, such as the myoepithelialcells lining the sweat gland, that contract to extrude liquidonto the skin surface during thermoregulation, as well as thearrector pili muscle, which attaches to the hair follicle andis responsible for creating goose bumps when the body’score temperature falls (14).
Adult skin is also home to at least 2 different neural crestcell populations: the melanocyte, which provides pigmentationand UV protection to human epidermis and color to the hair shaft(15), and the Merkel cell, a neuroendocrine cell responsiblefor transmission of touch sensation through the cutaneous nerves,among other functions (Figure 1) (16). There are also significantanatomical variations in skin structure on different parts ofthe body, such as the thick, protective epidermis on the palmsand soles compared with the thin skin on the eyelid, and specializedregions without hair follicles, such as the glabrous (lip) epithelium,or with a high density of hair follicles, such as the scalp.
Thus the skin you’re in is a highly specialized and meticulouslyregulated organ system populated by numerous different celltypes that each contribute uniquely to its multitude of functions(6). Likewise, the spectrum of skin disorders that arise whenthese functions go awry is virtually limitless. The skin-relatedReviews in this series focus on 4 main topics: the epidermalbarrier, autoimmune skin disease, epithelial viral infection,and the relationship between the skin and the central nervoussystem.