The NFκB-inducing kinase is essential for the developmental programming of skin-resident and IL-17-producing γδ T cells

gamma delta T cells contribute to first line immune defense, particularly through their ability for rapid production of proinflammatory cytokines. The cytokine profile of gamma delta T cells is hard-wired already during thymic development. Yet, the molecular pathways underlying this phenomenon are incompletely understood. Here we show that signaling via the NF kappa B-inducing kinase (NIK) is essential for the formation of a fully functional gamma delta T cell compartment. In the absence of NIK, development of V gamma 5(+) dendritic epidermal T cells (DETCs) was halted in the embryonic thymus, and impaired NIK function caused a selective loss of IL-17 expression by gamma delta T cells. Using a novel conditional mutant of NIK, we could show in vivo that NIK signaling in thymic epithelial cells is essential for the thymic hardwiring of gamma delta T cell cytokine production.