Taking the lead - how keratinocytes orchestrate skin T cell immunity

The skin comprises a complex coordinated system of epithelial tissue cells and immune cells that ensure adequate immune reactions against trauma, toxins and pathogens, while maintaining tissue homeostasis. Keratinocytes form the outermost barrier of the skin, and sense changes in barrier integrity, intrusion of microbial components and stress molecules. Thus, they act as sentinels that continuously communicate the status of the organ to the cutaneous immune system. Upon damage the keratinocytes initiate a pro-inflammatory signaling cascade that leads to the activation of resident immune cells. Simultaneously, the tissue mediates and supports immune-suppressive functions to contain inflammation locally. After resolution of inflammation, the skin provides a niche for regulatory and effector memory T cells that can quickly respond to reoccurring antigens. In this review we discuss the central role of keratinocyte-derived signals in controlling cutaneous T cell immunity.