Restricted Expression of the Thymoproteasome Is Required for Thymic Selection and Peripheral Homeostasis of CD8+ T Cells

Tomaru, Utano; Konno, Saori; Miyajima, Syota; Kimoto, Rikuto; Onodera, Mari; Kiuchi, Shizuka; Murata, Shigeo; Ishizu, Akihiro; Kasahara, Masanori

Restricted Expression of the Thymoproteasome Is Required for Thymic Selection and Peripheral Homeostasis of CD8+ T Cells

Tomaru, Utano; Konno, Saori; Miyajima, Syota et al.

Cell Reports, 2019, 26(3), 639-651

Permalink : https://hdl.handle.net/2115/73289

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アクセス権	open access
URI	https://hdl.handle.net/2115/73289
タイトル	Restricted Expression of the Thymoproteasome Is Required for Thymic Selection and Peripheral Homeostasis of CD8+ T Cells
著者	Tomaru, Utano ; Konno, Saori ; Miyajima, Syota ; Kimoto, Rikuto ; Onodera, Mari ; Kiuchi, Shizuka ; Murata, Shigeo ; Ishizu, Akihiro ; Kasahara, Masanori
e-Rad_Researcher 20360901 著者名 Tomaru, Utano
著者名 Konno, Saori
著者名 Miyajima, Syota
著者名 Kimoto, Rikuto
著者名 Onodera, Mari
著者名 Kiuchi, Shizuka
著者名 Murata, Shigeo
e-Rad_Researcher 60321957 著者名 Ishizu, Akihiro
e-Rad_Researcher 30241318 著者名 Kasahara, Masanori
言語	英語
キーワード	thymoproteasome
	proteasome
	thymic epithelial cells
	thymic selection
	naïve T cells
	memory T cells
	self peptide
	autoimmune disease
	autoimmunity
発行日	2019-01-15
出版者	Cell Press
収録物名	Cell Reports
巻(号)	26(3)
ページ	639-651
抄録	The thymoproteasome subunit β5t is specifically expressed in cortical thymic epithelial cells (TECs) and generates unique peptides to support positive selection. In this study, using a mouse model ubiquitously expressing β5t, we showed that aberrant expression of self-peptides generated by β5t affects CD8+ T cell homeostasis, including thymic selection and maintenance of the peripheral naive pool of CD8+ T cells. In mice in which β5t was expressed both in cortical and medullary TECs, the abundance of CD8+ lineage thymocytes was reduced, and extra-thymic expression of β5t caused accumulation of CD8+ T cells with the memory or exhausted phenotype and induced autoreactive T cell responses. We found that thymoproteasomes are essential for positive selection but that the subsequent change in peptide repertoire in the medulla is also crucial for thymic selection and that β5t-derived peptide must be confined to the thymus to avoid autoimmunity in peripheral tissues.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
PISSN	2211-1247
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1016/j.celrep.2018.12.078