ABSTRACT Support is requested for a Keystone Symposia conference entitled Skin Health and Disease: Immune, Epithelial and Microbiome Crosstalk, organized by Drs. Michel Gilliet, Emma Guttman, Anthony Oro and Manolis Pasparakis. The conference will be held in Hannover, Germany from April 8-11, 2019. The skin is the largest human organ and the primary interface between the body and the environment. It provides the first line of defense against invading pathogens and trauma via its physical barrier properties but also via active defense mechanisms orchestrated by a coordinated interplay between epithelial and immune cells. Recently, the skin microbiota has emerged as an important third player that critically influences skin homeostasis and inflammation by interacting with epithelial and immune cells. This conference highlights these reciprocal interactions and describe their impact on skin physiology and pathophysiology. A central focus will be to discuss how the composition of the skin microbiota regulates homeostasis and determines susceptibility to inflammatory, allergic and neoplastic diseases of the skin and other epithelial tissues. Emerging concepts regarding the mechanisms influencing the epithelial-immune-microbiota crosstalk and opportunities for therapeutic interventions will be discussed. The conference will provide a unique setting for in-depth, cross- disciplinary discussions between basic skin scientists and biologists studying immune responses in other barrier organs, dermatologists, cancer biologists, immunologists, and many researchers from disparate fields who normally do not have opportunities to meet. This conference will also foster interaction with potential industry partners, who increasingly see the skin as a major focus for gaining insights into immune mechanisms and for development of targeted therapies for patients with chronic inflammatory diseases, allergic diseases and cancer. Finally, the conference will promote the scientific and professional development of all attendees, with a special emphasis on trainees and early-career scientists.