The thymic cortical epithelium determines the TCR repertoire of IL-17-producing γδT cells

The thymus provides a specialized microenvironment in which distinct subsets of thymic epithelial cells (TECs) support T-cell development. Here, we describe the significance of cortical TECs (cTECs) in T-cell development, using a newly established mouse model of cTEC deficiency. The deficiency of mature cTECs caused a massive loss of thymic cellularity and impaired the development of gamma delta T cells and invariant natural killer T cells. Unexpectedly, the differentiation of certain gamma delta T-cell subpopulationsinterleukin-17-producing V gamma 4 and V gamma 6 cellswas strongly dysregulated, resulting in the perturbation of gamma delta T-mediated inflammatory responses in peripheral tissues. These findings show that cTECs contribute to the shaping of the TCR repertoire, not only of conventional T cells but also of inflammatory innate alpha beta T cells.