Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-tolerance.
Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-tolerance.
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DOI：
10.1084/jem.20080046
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发表时间：
2008-11-24
影响因子：
15.3
通讯作者：
Matsumoto, Mitsuru
中科院分区：
文献类型：
--
作者：
Yano, Masashi;Kuroda, Noriyuki;Han, Hongwei;Meguro-Horike, Makiko;Nishikawa, Yumiko;Kiyonari, Hiroshi;Maemura, Kentaro;Yanagawa, Yuchio;Obata, Kunihiko;Takahashi, Satoru;Ikawa, Tomokatsu;Satoh, Rumi;Kawamoto, Hiroshi;Mouri, Yasuhiro;Matsumoto, Mitsuru
自身免疫调节因子（Aire）在髓质胸腺上皮细胞（髓质胸腺上皮细胞[mTECs]）的组织限制性抗原（TRA）基因的不同阵列表达中以及在胸腺微环境的组织中的作用是谜。我们通过创建一种小鼠品系来解决这个问题，其中将绿色荧光蛋白（GFP）的编码序列插入Aire基因座，从而同时破坏功能性Aire蛋白表达。我们发现，Aire+（即，GFP+）mTEC是负责Aire依赖性TRA基因（如胰岛素2和唾液蛋白1）表达的主要细胞类型，而Aire非依赖性TRA基因（如C-反应蛋白和谷氨酸脱羧酶67）则由Aire+和Aire− mTEC表达。值得注意的是，从mTECs的Aire的情况下，造成形态学的变化，以及改变分布的mTECs致力于Aire的表达。此外，我们发现，表达外皮蛋白（终末表皮分化的标志物）的mTEC的数量在Aire缺陷小鼠胸腺中减少，这与髓质中几乎没有Hassall小体样结构有关。我们的研究结果表明，Aire控制mTEC的分化程序，从而组织全球mTEC的完整性，使TRA表达从胸腺微环境中的终末分化的mTEC。
The roles of autoimmune regulator (Aire) in the expression of the diverse arrays of tissue-restricted antigen (TRA) genes from thymic epithelial cells in the medulla (medullary thymic epithelial cells [mTECs]) and in organization of the thymic microenvironment are enigmatic. We approached this issue by creating a mouse strain in which the coding sequence of green fluorescent protein (GFP) was inserted into the Aire locus in a manner allowing concomitant disruption of functional Aire protein expression. We found that Aire+ (i.e., GFP+) mTECs were the major cell types responsible for the expression of Aire-dependent TRA genes such as insulin 2 and salivary protein 1, whereas Aire-independent TRA genes such as C-reactive protein and glutamate decarboxylase 67 were expressed from both Aire+ and Aire− mTECs. Remarkably, absence of Aire from mTECs caused morphological changes together with altered distribution of mTECs committed to Aire expression. Furthermore, we found that the numbers of mTECs that express involucrin, a marker for terminal epidermal differentiation, were reduced in Aire-deficient mouse thymus, which was associated with nearly an absence of Hassall's corpuscle-like structures in the medulla. Our results suggest that Aire controls the differentiation program of mTECs, thereby organizing the global mTEC integrity that enables TRA expression from terminally differentiated mTECs in the thymic microenvironment.
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基因剂量 - AIR在胸腺表达，克隆缺失和器官特异性自身免疫性中的限制作用。
影响因子：
15.3
作者：
Liston, A;Gray, DHD;Lesage, S;Fletcher, AL;Wilson, J;Webster, KE;Scott, HS;Boyd, RL;Peltonen, L;Goodnow, CC
通讯作者：
Goodnow, CC
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：
30.5
作者：
Derbinski, J;Schulte, A;Klein, L
通讯作者：
Klein, L
影响因子：
56.9
作者：
Anderson, MS;Venanzi, ES;Mathis, D
通讯作者：
Mathis, D
影响因子：
4.8
作者：
Akiyoshi, H;Hatakeyama, S;Matsumoto, M
通讯作者：
Matsumoto, M