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

Takeshi Nitta; Ryunosuke Muro; Yukiko Shimizu; Sachiko Nitta; Hiroyo Oda; Yuki Ohte; Motohito Goto; Rieko Yanobu-Takanashi; Tomoya Narita; Hiroshi Takayanagi; Hisataka Yasuda; Tadashi Okamura; Shigeo Murata; Harumi Suzuki

doi:10.15252/embr.201540096

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

EMBO Rep. 2015 May;16(5):638-53. doi: 10.15252/embr.201540096. Epub 2015 Mar 13.

Authors

Affiliations

¹ Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Chiba, Japan.
² Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
³ Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
⁴ Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
⁵ Bioindustry Division, Oriental Yeast Co., Ltd., Tokyo, Japan.
⁶ 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.
⁷ Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, Chiba, Japan hsuzuki@ri.ncgm.go.jp.

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.

Keywords: IL‐17; thymic epithelial cell; thymus; β5t; γδT.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Cell Survival / genetics
DNA Mutational Analysis
Epithelial Cells / cytology
Epithelial Cells / metabolism
Epithelium / immunology
Epithelium / metabolism*
Female
Inflammation / genetics
Inflammation / immunology
Inflammation / metabolism
Interleukin-17 / biosynthesis*
Mice
Mice, Knockout
Mice, Transgenic
Mutation
Natural Killer T-Cells / immunology
Natural Killer T-Cells / metabolism
Proteasome Endopeptidase Complex / genetics
Proteasome Endopeptidase Complex / metabolism
Receptors, Antigen, T-Cell / genetics
Receptors, Antigen, T-Cell / metabolism*
Receptors, Antigen, T-Cell, gamma-delta / genetics
Receptors, Antigen, T-Cell, gamma-delta / metabolism*
T-Lymphocyte Subsets / cytology
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism*
Thymocytes / cytology
Thymocytes / immunology
Thymocytes / metabolism
Thymus Gland / immunology
Thymus Gland / metabolism*
Thymus Gland / pathology

Substances

Interleukin-17
Receptors, Antigen, T-Cell
Receptors, Antigen, T-Cell, gamma-delta
Proteasome Endopeptidase Complex