Increased Production of IL-17A-Producing γδ T Cells in the Thymus of Filaggrin-Deficient Mice

Mutations in the filaggrin gene (Flg) are associated with increased systemic levels of Th17 cells and increased IL-17A production following antigen exposure in both humans and mice. In addition to Th17 cells, gamma delta T cells can produce IL-17A. The differentiation of gamma delta T cells to either IFN gamma or IL-17A-producing (gamma delta T17) cells is mainly determined in the thymus. Interestingly, it has been reported that filaggrin is expressed in the Hassall bodies in the human thymic medulla. However, whether filaggrin affects gamma delta T cell development is not known. Here, we show that filaggrin-deficient flaky tail (ft/ft) mice have an increased number of gamma delta T17 cells in the spleen, epidermis, and thymus compared to wild-type (WT) mice. We demonstrate that filaggrin is expressed in the mouse thymic medulla and that blocking the egress of cells from the thymus results in accumulation of V gamma(2+) gamma delta T17 cells in the thymus of adult ft/ft mice. Finally, we find increased T cell receptor expression levels on gamma delta T cells and increased levels of IL-6 and IL-23 in the thymus of ft/ft mice. These findings demonstrate that filaggrin is expressed in the mouse thymic medulla and that production of V gamma(2+) gamma delta T17 cells is dysregulated in filaggrin-deficient ft/ft mice.