AUTHOR=Jee Mia Hamilton , Johansen Jeanne Duus , Buus Terkild Brink , Petersen Trine Hilkjær , Gadsbøll Anne-Sofie Østergaard , Woetmann Anders , Ødum Niels , Thyssen Jacob Pontoppidan , White Andrea Jane , Anderson Graham , Geisler Carsten , Bonefeld Charlotte Menné 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00988

DOI=10.3389/fimmu.2018.00988

ISSN=1664-3224

ABSTRACT=<p>Mutations in the filaggrin gene (<italic>Flg</italic>) 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, γδ T cells can produce IL-17A. The differentiation of γδ T cells to either IFNγ or IL-17A-producing (γδT17) 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 γδ T cell development is not known. Here, we show that filaggrin-deficient flaky tail (<italic>ft/ft</italic>) mice have an increased number of γδT17 cells in the spleen, epidermis, and thymus compared to wild-type (<italic>WT</italic>) 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 Vγ2<sup>+</sup> γδT17 cells in the thymus of adult <italic>ft/ft</italic> mice. Finally, we find increased T cell receptor expression levels on γδ T cells and increased levels of IL-6 and IL-23 in the thymus of <italic>ft/ft</italic> mice. These findings demonstrate that filaggrin is expressed in the mouse thymic medulla and that production of Vγ2<sup>+</sup> γδT17 cells is dysregulated in filaggrin-deficient <italic>ft/ft</italic> mice.</p>