title: The thymic cortical epithelium determines the TCR repertoire of IL-17-producing γδT cells.
abstract: 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 αβT cells and invariant natural killer T cells. Unexpectedly, the differentiation of certain γδT-cell subpopulations-interleukin-17-producing Vγ4 and Vγ6 cells-was strongly dysregulated, resulting in the perturbation of γδT-mediated inflammatory responses in peripheral tissues. These findings show that cTECs contribute to the shaping of the TCR repertoire, not only of "conventional" αβT cells but also of inflammatory "innate" γδT cells.
authors.affiliation: Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nitta
authors.affiliation: Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: Ryunosuke
authors.initials: R
authors.lastname: Muro
authors.affiliation: Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Nitta
authors.affiliation: Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Oda
authors.affiliation: Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ohte
authors.affiliation: Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Motohito
authors.initials: M
authors.lastname: Goto
authors.affiliation: Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Yanobu-Takanashi
authors.affiliation: Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Narita
authors.affiliation: Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takayanagi
authors.affiliation: Bioindustry Division, Oriental Yeast Co., Ltd., Tokyo, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Yasuda
authors.affiliation: Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan Section of Animal Models, Department of Infectious Diseases, Research Institute National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murata
authors.affiliation: Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Chiba, Japan hsuzuki@ri.ncgm.go.jp.
authors.forename: Harumi
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival / Q000235:genetics; D004252:DNA Mutational Analysis; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D004848:Epithelium / Q000276:immunology / Q000378:metabolism*; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D060168:Thymocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D020381:Interleukin-17; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D046988:Proteasome Endopeptidase Complex
keywords: IL‐17; thymic epithelial cell; thymus; β5t; γδT