Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation

Nishikawa, Yumiko; Hirota, Fumiko; Yano, Masashi; Kitajima, Hiroyuki; Miyazaki, Jun-ichi; Kawamoto, Hiroshi; Mouri, Yasuhiro; Matsumoto, Mitsuru

doi:https://doi.org/10.1084/jem.20092144

このアイテムのアクセス数:196件（2022-09-29 14:11 集計）

このアイテムへのリンクには次のURLをご利用ください: https://hdl.handle.net/11094/23113

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論文情報

タイトル	Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation
著者	NRID 1000060448214 1000060448214 著者名 Nishikawa, Yumiko
	著者名 Hirota, Fumiko
	NRID 1000010531858 1000010531858 著者名 Yano, Masashi
	NRID 1000090314905 1000090314905 著者名 Kitajima, Hiroyuki
	NRID 1000080229830 1000080229830 著者名 Miyazaki, Jun-ichi
	NRID 1000000343228 1000000343228 著者名 Kawamoto, Hiroshi
	NRID 1000080464353 1000080464353 著者名 Mouri, Yasuhiro
	NRID 1000060221595 1000060221595 著者名 Matsumoto, Mitsuru
抄録	The roles of autoimmune regulator (Aire)–expressing medullary thymic epithelial cells (mTECs) in the organization of the thymic microenvironment for establishing self-tolerance are enigmatic. We sought to monitor the production and maintenance of Aire-expressing mTECs by a fate-mapping strategy in which bacterial artificial chromosome transgenic (Tg) mice expressing Cre recombinase under the control of the Aire regulatory element were crossed with a GFP reporter strain. We found that, in addition to its well recognized expression within mature mTECs, Aire was expressed in the early embryo before emergence of the three germ cell layers. This observation may help to explain the development of ectodermal dystrophy often seen in patients with AIRE deficiency. With the use of one Tg line in which Cre recombinase expression was confined to mTECs, we found that Aire+CD80high mTECs further progressed to an Aire−CD80intermediate stage, suggesting that Aire expression is not constitutive from after its induction until cell death but instead is down-regulated at the beginning of terminal differentiation. We also demonstrated that many mTECs of Aire-expressing lineage are in close contact with thymic dendritic cells. This close proximity may contribute to transfer of tissue-restricted self-antigens expressed by mTECs to professional antigen-presenting cells.
出版者	The Rockefeller University Press
収録物名	Journal of Experimental Medicine
巻	207
号	5
開始ページ	963
終了ページ	971
刊行年月	2010-04-19
言語	英語
ハンドルURL	https://hdl.handle.net/11094/23113
ISSN	00221007
NCID	AA00697559
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1084/jem.20092144
アクセス権	open access
権利情報	© 2010 Nishikawa et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial– Share Alike 3.0 Unported license, as described at http://creativecommons .org/licenses/by-nc-sa/3.0/).
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Journal of Experimental Medicine.207(5) p.963-p.971
DC.title	Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation
DC.creator	Nishikawa, Yumiko
	Hirota, Fumiko
	Yano, Masashi
	Kitajima, Hiroyuki
	Miyazaki, Jun-ichi
	Kawamoto, Hiroshi
	Mouri, Yasuhiro
	Matsumoto, Mitsuru
DC.publisher	The Rockefeller University Press
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2010-04-19
DC.identifier	https://doi.org/10.1084/jem.20092144
DCTERMS.abstract	The roles of autoimmune regulator (Aire)–expressing medullary thymic epithelial cells (mTECs) in the organization of the thymic microenvironment for establishing self-tolerance are enigmatic. We sought to monitor the production and maintenance of Aire-expressing mTECs by a fate-mapping strategy in which bacterial artificial chromosome transgenic (Tg) mice expressing Cre recombinase under the control of the Aire regulatory element were crossed with a GFP reporter strain. We found that, in addition to its well recognized expression within mature mTECs, Aire was expressed in the early embryo before emergence of the three germ cell layers. This observation may help to explain the development of ectodermal dystrophy often seen in patients with AIRE deficiency. With the use of one Tg line in which Cre recombinase expression was confined to mTECs, we found that Aire+CD80high mTECs further progressed to an Aire−CD80intermediate stage, suggesting that Aire expression is not constitutive from after its induction until cell death but instead is down-regulated at the beginning of terminal differentiation. We also demonstrated that many mTECs of Aire-expressing lineage are in close contact with thymic dendritic cells. This close proximity may contribute to transfer of tissue-restricted self-antigens expressed by mTECs to professional antigen-presenting cells.
DC.rights	© 2010 Nishikawa et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial– Share Alike 3.0 Unported license, as described at http://creativecommons .org/licenses/by-nc-sa/3.0/).
DC.format	application/pdf
citation_title	Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation
citation_author	Nishikawa, Yumiko
	Hirota, Fumiko
	Yano, Masashi
	Kitajima, Hiroyuki
	Miyazaki, Jun-ichi
	Kawamoto, Hiroshi
	Mouri, Yasuhiro
	Matsumoto, Mitsuru
citation_publisher	The Rockefeller University Press
citation_language	英語
citation_date	2010-04-19
citation_journal_title	Journal of Experimental Medicine
citation_volume	207
citation_issue	5
citation_firstpage	963
citation_lastpage	971
citation_issn	00221007
citation_doi	https://doi.org/10.1084/jem.20092144
citation_public_url	https://hdl.handle.net/11094/23113

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