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首页> 外文期刊>International Immunology >Regeneration of the adult thymus is preceded by the expansion of K5+K8+ epithelial cell progenitors and by increased expression of Trp63, cMyc and Tcf3 transcription factors in the thymic stroma
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Regeneration of the adult thymus is preceded by the expansion of K5+K8+ epithelial cell progenitors and by increased expression of Trp63, cMyc and Tcf3 transcription factors in the thymic stroma

机译：成年胸腺的再生先于K5 + K8 + 上皮细胞祖细胞的扩增以及Trp63，cMyc和Tcf3转录因子在胸腺基质中的表达增加

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Studies of HIV-1-infected individuals on anti-retroviral therapies and of patients receiving lymphoablating treatments indicate that the thymus retains restorative capacity even in adults. The contributions of the thymic epithelial cells (TECs) to the regeneration of the thymus and the identity of epithelial cell progenitors were evaluated in murine models of transient thymic atrophy followed by a complete regeneration. Using microarray approach, we analyzed the pattern of gene expression in TECs sorted from mice that were depleted of thymocytes by steroid treatment or by irradiation. The initial analysis identified significant increases in the mRNA for cMyc, Trp63 and Tcf3 transcription factors known to be expressed in early epithelial cell progenitors in tissues other than the thymus. Immunohistochemistry showed that in involuted thymuses, the cMyc and Trp63 proteins were expressed in a subset of cortical thymic epithelial cells (cTECs) that were keratin 5 positive (K5+), typifying cTEC precursors. Importantly, confocal microscopy established that epithelial cells with the phenotype of putative TEC progenitors (i.e. K5+K8+) expressed the Trp63 protein and confirmed that K5+K8+ TEC progenitors expanded significantly during atrophy and prior to the thymic regeneration. Thus, our data demonstrated for the first time that critical steps in the recovery of the adult thymus include expansion of TEC progenitors and elevated expression of Trp63, cMyc and Tcf3 transcription factors in the thymic stroma. These results suggest that TEC progenitors could be reactivated in the adult thymus and, therefore, reactivation of TEC progenitors could provide a new approach for thymic reconstitution.
机译：对受HIV-1感染的个体进行抗逆转录病毒疗法的研究以及接受淋巴切除治疗的患者的研究表明，即使在成年人中，胸腺仍具有恢复能力。胸腺上皮细胞（TECs）对胸腺再生的贡献和上皮细胞祖细胞的身份在短暂胸腺萎缩然后完全再生的小鼠模型中进行了评估。使用微阵列方法，我们分析了在通过类固醇治疗或辐射去除了胸腺细胞的小鼠中分类的TECs中的基因表达模式。初步分析确定了cMyc，Trp63和Tcf3转录因子的mRNA的显着增加，已知这些转录因子在除胸腺以外的组织中的早期上皮细胞祖细胞中表达。免疫组织化学研究显示，在退化的胸腺中，cMyc和Trp63蛋白在角蛋白5阳性（K5 + ）的皮质胸腺上皮细胞（cTECs）中表达，是cTEC的前体。重要的是，共聚焦显微镜确定了具有假定TEC祖细胞表型的上皮细胞（即K5 + K8 + ）表达Trp63蛋白并证实了K5 + K8 + TEC祖细胞在萎缩期间和胸腺再生之前显着扩增。因此，我们的数据首次证明了恢复成年胸腺的关键步骤包括TEC祖细胞的扩增以及胸腺基质中Trp63，cMyc和Tcf3转录因子的表达升高。这些结果表明，TEC祖细胞可以在成人胸腺中重新激活，因此，TEC祖细胞的重新激活可以为胸腺重构提供新的方法。

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  • 来源
    《International Immunology》 |2007年第11期|1249-1260|共12页
  • 作者

    Ileana Popa1 Iryna Zubkova1 Mario Medvedovic2 Tatiana Romantseva1 Howard Mostowski3 Richard Boyd4 and Marina Zaitseva1;

  • 作者单位

    Division of Viral Products Center for Biologics Evaluation and Research Food and Drug Administration 8800 Rockville Pike Bethesda MD 20892 USA;

    Department of Environmental Health University of Cincinnati Cincinnati OH 45267 USA;

    Division of Cellular and Gene Therapies Center for Biologics Evaluation and Research Food and Drug Administration 8800 Rockville Pike Bethesda MD 20892 USA;

    Monash Immunology and Stem Cell Laboratories Monash University Melbourne Australia;

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