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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://doi.org/10.1084/jem.20092144
このアイテムへのリンクには次のURLをご利用ください:http://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
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
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
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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