Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation.
Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation.
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DOI：
10.1084/jem.20092144
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发表时间：
2010-05-10
期刊：
影响因子：
--
通讯作者：
Matsumoto M
中科院分区：
文献类型：
--
作者：
Nishikawa Y;Hirota F;Yano M;Kitajima H;Miyazaki J;Kawamoto H;Mouri Y;Matsumoto M
表达自身免疫调节因子（Aire）的胸腺髓质上皮细胞（mTECs）在胸腺微环境组织中建立自身耐受的作用是谜。我们试图监测生产和维护的Aire表达mTEC的命运映射策略，其中细菌人工染色体转基因（Tg）小鼠表达Cre重组酶的控制下的Aire调控元件与GFP报告菌株杂交。我们发现，除了在成熟的mTECs中的公认表达外，Aire在三个生殖细胞层出现之前的早期胚胎中表达。这一观察结果可能有助于解释AIRE缺乏症患者中常见的外胚层营养不良的发展。通过使用Cre重组酶表达仅限于mTECs的一个Tg系，我们发现Aire+CD80high mTECs进一步发展到Aire− CD80中间阶段，表明Aire表达从诱导后直到细胞死亡不是组成型的，而是在终末分化开始时下调。我们还证明了许多表达Aire的mTEC与胸腺树突状细胞密切接触。这种紧密的接近可能有助于将mTEC表达的组织限制性自身抗原转移到专职抗原呈递细胞。
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.
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DOI：
10.1126/science.1159407
发表时间：
2008-08-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gardner JM;Devoss JJ;Friedman RS;Wong DJ;Tan YX;Zhou X;Johannes KP;Su MA;Chang HY;Krummel MF;Anderson MS
通讯作者：
Anderson MS
DOI：
10.4049/jimmunol.181.8.5225
发表时间：
2008-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Dooley J;Erickson M;Farr AG
通讯作者：
Farr AG
DOI：
10.1084/jem.20070795
发表时间：
2007-10-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gray D;Abramson J;Benoist C;Mathis D
通讯作者：
Mathis D
影响因子：
56.9
作者：
Anderson, MS;Venanzi, ES;Mathis, D
通讯作者：
Mathis, D
DOI：
10.1084/jem.20041457
发表时间：
2004-10-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gallegos AM;Bevan MJ
通讯作者：
Bevan MJ