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:info:doi/10.1084/jem.20092144

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タイトル	Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation
著者	Nishikawa, Yumiko Nishikawa, Yumiko
	Hirota, Fumiko Hirota, Fumiko
	Yano, Masashi Yano, Masashi
	Kitajima, Hiroyuki Kitajima, Hiroyuki
	Miyazaki, Jun-ichi Miyazaki, Jun-ichi
	Kawamoto, Hiroshi Kawamoto, Hiroshi
	Mouri, Yasuhiro Mouri, Yasuhiro
	Matsumoto, Mitsuru 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.
公開者	The Rockefeller University Press
掲載誌名	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
ISSN	00221007
NCID	AA00697559
DOI (出版社版)	info:doi/10.1084/jem.20092144
URL	http://hdl.handle.net/11094/23113
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/).
言語	英語
カテゴリ	学術雑誌論文 Journal Article

著者版フラグ	publisher
NII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
DCTERMS.issued" scheme="DCTERMS.W3CDTF	2010-04-19
DC.identifier	info:doi/10.1084/jem.20092144
DC.identifier" scheme="DCTERMS.URI	http://hdl.handle.net/11094/23113
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/).
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	info:doi/10.1084/jem.20092144
citation_public_url	http://hdl.handle.net/11094/23113

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