Identification of IL-7-Producing Cells in Primary and Secondary Lymphoid Organs Using IL-7-GFP Knock-In Mice
Identification of IL-7-Producing Cells in Primary and Secondary Lymphoid Organs Using IL-7-GFP Knock-In Mice
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DOI：
10.4049/jimmunol.1200586
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发表时间：
2012-08-15
影响因子：
4.4
通讯作者：
Ikuta, Koichi
中科院分区：
文献类型：
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作者：
Hara, Takahiro;Shitara, Soichiro;Ikuta, Koichi
IL-7是一种细胞因子，对淋巴细胞和其他造血细胞的发育和维持至关重要。然而，表达IL-7的细胞如何分布在淋巴器官中尚不清楚。为了解决这个问题，我们建立并分析了IL-7-GFP基因敲入小鼠。胸腺上皮细胞（TEC）在皮质和髓质中表达高水平的GFP，如用抗GFP抗体检测到的。胸腺间充质细胞也表达GFP。流式细胞术分析表明，皮质TEC表达更高的GFP水平比髓质TEC。在骨髓中，免疫组织化学显示在许多VCAM-1（+）间充质基质细胞和一些VCAM-1（-）细胞中有高水平的GFP。此外，通过流式细胞术检测，一半的VCAM-1（+）CD 31（-）基质细胞和一些血小板衍生生长因子受体α（+）基质细胞为GFP（+）。此外，我们还检测到GFP在T细胞区和淋巴结皮质嵴的成纤维网状细胞中的表达。值得注意的是，淋巴管内皮细胞（LEC）表达GFP在淋巴结髓质，皮肤表皮和肠组织中的高水平。此外，我们在分离的LEC中检测到丰富的IL-7转录本，表明LEC产生IL-7，这是迄今为止未知的发现。此外，GFP在肠上皮细胞亚群中表达，并且在葡聚糖硫酸钠诱导的急性结肠炎模型中该表达显著上调。总体而言，IL-7-GFP敲入小鼠作为一种独特的和强大的工具，检查IL-7表达细胞的身份和分布在体内。免疫学杂志，2012，189：1577-1584。
IL-7 is a cytokine crucial for development and maintenance of lymphocytes and other hematopoietic cells. However, how IL-7-expressing cells are distributed in lymphoid organs is not well known. To address this question, we established and analyzed IL-7-GFP knock-in mice. Thymic epithelial cells (TECs) expressed high GFP levels in the cortex and medulla, as detected with an anti-GFP Ab. Thymic mesenchymal cells also expressed GFP. Flow cytometry analysis suggested that cortical TECs expressed higher GFP levels than did medullary TECs. In bone marrow, immunohistochemistry indicated high levels of GFP in many VCAM-1(+) mesenchymal stromal cells and in some VCAM-1(-) cells. Additionally, half of the VCAM-1(+)CD31(-) stromal cells and some platelet-derived growth factor receptor alpha(+) stromal cells were GFP(+), as detected by flow cytometry. Moreover, we detected GFP expression in fibroblastic reticular cells in the T cell zone and cortical ridge of lymph nodes. Remarkably, lymphatic endothelial cells (LECs) expressed GFP at high levels within the lymph node medulla, skin epidermis, and intestinal tissues. Additionally, we detected abundant IL-7 transcripts in isolated LECs, suggesting that LECs produce IL-7, a heretofore unknown finding. Furthermore, GFP is expressed in a subpopulation of intestinal epithelial cells, and that expression was markedly upregulated in a dextran sulfate sodium-induced acute colitis model. Overall, IL-7-GFP knock-in mice serve as a unique and powerful tool to examine the identity and distribution of IL-7-expressing cells in vivo. The Journal of Immunology, 2012, 189: 1577-1584.