Cutting Edge: A Thymocyte-Thymic Epithelial Cell Cross-Talk Dynamically Regulates Intrathymic IL-7 Expression In Vivo
Cutting Edge: A Thymocyte-Thymic Epithelial Cell Cross-Talk Dynamically Regulates Intrathymic IL-7 Expression In Vivo
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DOI：
10.4049/jimmunol.1000601
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发表时间：
2010-06-01
影响因子：
4.4
通讯作者：
Di Santo, James P.
中科院分区：
文献类型：
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作者：
Alves, Nuno L.;Huntington, Nicholas D.;Di Santo, James P.
胸腺上皮细胞（TEC）是胸腺内必需的胸腺生成素IL-7的主要来源。胸腺细胞-TEC相互作用是否在IL-7表达的调节中起作用尚不清楚。通过利用IL-7报告小鼠（其中黄色荧光蛋白表达识别表达高水平IL-7的TEC（Il 7（+）TEC），我们表明Il 7（+）TEC在胸腺器官发生期间与新出现的髓质TEC分离。尽管IL 7（+）TEC通常随着年龄的增长而减少，但我们发现IL 7（+）TEC明显保留在淋巴样Rag 2（-/-）IL 2 rg（-/-）IL-7报告小鼠中，这些小鼠表现出严重的胸腺生成停滞。将Tcra（-/-）或野生型（但不是Rag 2（-/-））造血祖细胞转移到淋巴样IL-7报告受体使IL-7（+）TEC的频率正常化并重新建立皮质TEC/髓质TEC分离。虽然胸腺细胞来源的信号通常被认为是刺激TEC成熟，我们的研究结果确定了一个负反馈机制，其中来自TCR β选择的胸腺细胞的信号调节TEC依赖性IL-7的表达。免疫学杂志，2010，184：5949-5953。
Thymic epithelial cells (TECs) are the predominant intrathymic source of the essential thymopoietin IL-7. Whether thymocyte-TEC interactions have a role in the regulation of IL-7 expression is not known. By exploiting IL-7 reporter mice in which yellow fluorescent protein expression identifies TECs expressing high levels of IL-7 (Il7(+) TECs), we show that Il7(+) TECs segregate from emerging medullary TECs during thymic organogenesis. Although Il7(+) TECs normally diminish with age, we found that Il7(+) TECs are markedly retained in alymphoid Rag2(-/-) Il2rg(-/-) IL-7 reporter mice that manifest a profound thymopoietic arrest. Transfer of Tcra(-/-) or wild-type (but not Rag2(-/-)) hematopoietic progenitors to alymphoid IL-7 reporter recipients normalizes the frequency of Il7(+) TECs and re-establishes cortical TEC/medullary TEC segregation. Although thymocyte-derived signals are often considered stimulatory for TEC maturation, our findings identify a negative feedback mechanism in which signals derived from TCR beta-selected thymocytes modulate TEC-dependent IL-7 expression. The Journal of Immunology, 2010, 184: 5949-5953.