Characterization of the thymic IL-7 niche in vivo
Characterization of the thymic IL-7 niche in vivo
复制标题
DOI：
10.1073/pnas.0809559106
复制
发表时间：
2009-02-03
影响因子：
11.1
通讯作者：
Di Santo, James P.
中科院分区：
文献类型：
--
作者：
Alves, Nuno L.;Goff, Odile Richard-Le;Di Santo, James P.
胸腺代表T细胞发育的“摇篮”，胸腺基质为发育中的胸腺细胞提供多种可溶性和膜线索。虽然IL-7被认为是胸腺生成的重要因素，但胸腺IL-7活性的“环境生态位”在体内的特征仍然很差。使用细菌人工染色体转基因小鼠，其中YFP是在IL-7启动子的控制下，我们确定了一个子集的胸腺上皮细胞（TEC），共表达YFP和高水平的IL-7（hi）转录（IL-7（hi）细胞）。IL-7（hi）TEC在早期胎儿发育期间产生，在整个生命中持续存在，并且共表达对正常胸腺生成至关重要的稳态趋化因子（Ccl 19、Ccl 25、Cxcl 12）和细胞因子（IL 15）。在成年胸腺中，IL-7（hi）细胞定位于皮质-髓质交界处，并显示皮质和髓质TEC的特征。有趣的是，IL-7（hi）细胞的频率随着年龄的增长而下降，这表明与年龄相关的胸腺退化机制与IL-7水平下降有关。我们的时间-空间分析的IL-7产生细胞在胸腺在体内表明，胸腺IL-7水平的动态调节在不同的生理条件下。这种IL-7报告小鼠为进一步剖析体内控制胸腺IL-7表达的机制提供了有价值的工具。
The thymus represents the "cradle" for T cell development, with thymic stroma providing multiple soluble and membrane cues to developing thymocytes. Although IL-7 is recognized as an essential factor for thymopoiesis, the "environmental niche" of thymic IL-7 activity remains poorly characterized in vivo. Using bacterial artificial chromosome transgenic mice in which YFP is under control of IL-7 promoter, we identify a subset of thymic epithelial cells (TECs) that co-express YFP and high levels of Il7 transcripts (IL-7(hi) cells). IL-7(hi) TECs arise during early fetal development, persist throughout life, and co-express homeostatic chemokines (Ccl19, Ccl25, Cxcl12) and cytokines (Il15) that are critical for normal thymopoiesis. In the adult thymus, IL-7(hi) cells localize to the cortico-medullary junction and display traits of both cortical and medullary TECs. Interestingly, the frequency of IL-7(hi) cells decreases with age, suggesting a mechanism for the age-related thymic involution that is associated with declining IL-7 levels. Our temporal-spatial analysis of IL-7-producing cells in the thymus in vivo suggests that thymic IL-7 levels are dynamically regulated under distinct physiological conditions. This IL-7 reporter mouse provides a valuable tool to further dissect the mechanisms that govern thymic IL-7 expression in vivo.