The cytokine RANKL produced by positively selected thymocytes Fosters medullary thymic epithelial cells that express autoimmune regulator
The cytokine RANKL produced by positively selected thymocytes Fosters medullary thymic epithelial cells that express autoimmune regulator
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DOI：
10.1016/j.immuni.2008.06.018
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发表时间：
2008-09-19
期刊：
影响因子：
32.4
通讯作者：
Takahama, Yousuke
中科院分区：
文献类型：
--
作者：
Hikosaka, Yu;Nitta, Takeshi;Takahama, Yousuke
胸腺髓质提供了一个微环境，其中胸腺髓质上皮细胞（mTECs）表达自身免疫调节因子和多种组织限制性基因，有助于启动自身耐受。积极的选择是必不可少的胸腺髓质形成通过以前未知的机制。在这里，我们表明，细胞因子RANK配体（RANKL）产生的积极选择的胸腺细胞和调节mTEC的细胞性与RANK和骨保护素的相互作用。在缺乏阳性选择的小鼠中，RANKL的强制表达恢复了胸腺髓质，而RANKL扰动损害了髓质形成。这些结果表明，由阳性选择的胸腺细胞产生的RANKL负责促进胸腺髓质形成，从而建立中枢耐受。
The thymic medulla provides a microenvironment where medullary thymic epithelial cells (mTECs) express autoimmune regulator and diverse tissue-restricted genes, contributing to launching self-tolerance. Positive selection is essential for thymic medulla formation via a previously unknown mechanism. Here we show that the cytokine RANK ligand (RANKL) was produced by positively selected thymocytes and regulated the cellularity of mTEC by interacting with RANK and osteoprotegerin. Forced expression of RANKL restored thymic medulla in mice lacking positive selection, whereas RANKL perturbation impaired medulla formation. These results indicate that RANKL produced by positively selected thymocytes is responsible for fostering thymic medulla formation, thereby establishing central tolerance.