Neonatal-derived IL-17 producing dermal gd T cells are required to prevent spontaneous atopic dermatitis

Abstract

Atopic Dermatitis (AD) is a T cell-mediated chronic skin disease and is associated with altered skin barrier integrity. Infants with mutations in genes involved in tissue barrier fitness are predisposed towards inflammatory diseases, but most do not develop or sustain the diseases, suggesting that there exist regulatory immune mechanisms to repair tissues and/or prevent aberrant inflammation. The absence of one single murine dermal cell type, the innate neonatal-derived IL-17 producing {gamma}{delta} T (T{gamma}{delta}17) cells, from birth resulted in spontaneous, highly penetrant AD with all the major hallmarks of human AD. In T{gamma}{delta}17 cell-deficient mice, basal keratinocyte transcriptome was altered months in advance of AD induction. Fulminant disease is driven by skin commensal bacteria dysbiosis and highly expanded dermal {beta} T clonotypes that produce the type three cytokines, IL-17 and IL-22. These results demonstrate that neonatal T{gamma}{delta}17 cells are innate skin regulatory T cells. The bifurcation of type 3 cytokine producing skin T cells into the homeostatic, early innate and pathogen-sensing, late adaptive T cell compartments underpin healthy skin and accounts for the dual function of type 3 cytokines in skin maintenance and inflammation.