Relb acts downstream of medullary thymic epithelial stem cells and is essential for the emergence of RANK(+) medullary epithelial progenitors.
Relb acts downstream of medullary thymic epithelial stem cells and is essential for the emergence of RANK(+) medullary epithelial progenitors.
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DOI：
10.1002/eji.201546253
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发表时间：
2016-04
影响因子：
5.4
通讯作者：
Anderson, Graham
中科院分区：
文献类型：
--
作者：
Baik, Song;Sekai, Miho;Hamazaki, Yoko;Jenkinson, William E.;Anderson, Graham
胸腺上皮细胞（TEC）为αβT细胞发育提供必要信号，而髓质TEC（mTEC）通过阴性选择和Foxp 3+调节性T（Treg）细胞发育控制T细胞耐受。虽然异质性的mTEC车厢内进行了很好的研究，mTEC发展的特定阶段的分子调控仍然知之甚少。鉴于RANK‐RANKL轴在胸腺髓质形成中的重要性，我们使用RANK Venus报告小鼠分析了RANK+ TEC在发育过程中的个体发育以及RANK表达与SSEA‐1定义的mTEC干细胞的相关性。此外，我们还研究了关键监管机构Foxn 1和Relb的要求如何映射到mTEC开发的特定阶段。在这里，我们显示SSEA-1+ mTEC干细胞在RANK表达之前出现，并且存在于裸鼠和Relb −/−小鼠中，提供了mTEC谱系特化独立于Foxn 1和Relb发生的直接证据。相反，我们表明Relb对于下游RANK+ mTEC祖细胞的有效产生是必要的。总的来说，我们的工作定义了髓质发育过程中关键TEC调节器的特定阶段要求，包括Relb依赖性的时间，并提供了有关控制mTEC规格的机制的新信息。
Thymic epithelial cells (TECs) provide essential signals for αβT‐cell development, and medullary TECs (mTECs) control T‐cell tolerance through both negative selection and Foxp3+ regulatory T (Treg) cell development. Although heterogeneity within the mTEC compartment is well studied, the molecular regulators of specific stages of mTEC development are still poorly understood. Given the importance of the RANK‐RANKL axis in thymus medulla formation, we have used RANK Venus reporter mice to analyze the ontogeny of RANK+ TECs during development and correlated RANK expression with mTEC stem cells defined by SSEA‐1. In addition, we have investigated how requirements for the key regulators Foxn1 and Relb map to specific stages of mTEC development. Here, we show SSEA‐1+ mTEC stem cells emerge prior to RANK expression and are present in both nude and Relb −/− mice, providing direct evidence that mTEC lineage specification occurs independently of Foxn1 and Relb. In contrast, we show that Relb is necessary for the effective production of downstream RANK+ mTEC progenitors. Collectively, our work defines stage‐specific requirements for critical TEC regulators during medulla development, including the timing of Relb dependency, and provides new information on mechanisms controlling mTEC specification.
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影响因子：
7
作者：
Sansom SN;Shikama-Dorn N;Zhanybekova S;Nusspaumer G;Macaulay IC;Deadman ME;Heger A;Ponting CP;Holländer GA
通讯作者：
Holländer GA
影响因子：
5.4
作者：
Onder, Lucas;Nindl, Veronika;Ludewig, Burkhard
通讯作者：
Ludewig, Burkhard
影响因子：
8.8
作者：
Wong, Kahlia;Lister, Natalie L.;Chidgey, Ann P.
通讯作者：
Chidgey, Ann P.
影响因子：
32.4
作者：
Roberts NA;White AJ;Jenkinson WE;Turchinovich G;Nakamura K;Withers DR;McConnell FM;Desanti GE;Benezech C;Parnell SM;Cunningham AF;Paolino M;Penninger JM;Simon AK;Nitta T;Ohigashi I;Takahama Y;Caamano JH;Hayday AC;Lane PJ;Jenkinson EJ;Anderson G
通讯作者：
Anderson G
影响因子：
32.4
作者：
Ucar, Ahmet;Ucar, Olga;Klug, Paula;Matt, Sonja;Brunk, Fabian;Hofmann, Thomas G.;Kyewski, Bruno
通讯作者：
Kyewski, Bruno