Immunity at the surface: homeostatic mechanisms of the skin immune system

The coordinated function of multiple epidermal and dermal cell populations allows the skin immune system to respond rapidly and effectively to a wide variety of insults occurring at the interface of the organism and its environment. Keratinocytes are the first line of defense in the skin immune system, and keratinocyte-derived cytokines are pivotal in mobilizing leukocytes from blood and signaling other cutaneous cells. Cytokine-mediated cellular communication also enables dermal fibroblasts and endothelial cells lining the cutaneous vasculature to participate in immune and inflammatory responses. Skin is an important site for antigen presentation, and both epidermal Langerhans cells and dermal dendritic cells play pivotal roles in T cell-mediated immune responses to antigens encountered in skin. Proinflammatory signaling pathways are necessarily balanced by a variety of regulatory pathways that help maintain the homeostatic functioning of the skin immune system.