698 Capturing the role of epithelial-immune interactions to maintain tissue homeostasis

Abstract

The skin is an essential barrier that protects organisms from the external environment. Despite recent advances in our understanding of skin homeostasis, the ways by which diverse cell types interact with each other to sustain this process is not fully understood. Challenges in addressing this question have been the inability to simultaneously follow behaviors of different cell types and to define their functional interactions in a live mammal. Skin epidermis is an ideal system because of its accessibility and well-characterized epithelial and coexisting epidermal immune cells. Epithelial cells in the skin are intermixed with different types of immune cells such as dendritic epidermal T-cells (DETCs) and Langerhans cells (LCs). By using our intravital imaging platform, I have established novel genetic and cell biological approaches to define and manipulate epithelial-immune interactions in an intact epidermis in live mice. In addition to immune surveillance, our data shows that both immune populations can perceive and respond to the changes of their neighbors. Furthermore, epidermal immune cells retain spatial organization within their own population while neighboring epithelial cells continuously divide and differentiate. Lastly, skin epithelial cells act as regional checkpoints for the organization and number of epidermal immune populations, but not vice versa, during epidermal homeostasis. This study reveals new principles of immune organization within the epidermis, and elucidates dynamic epithelial-immune interactions that are in place to maintain homeostasis of the epidermis.