Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
J Immunol. 2013 Jun 15;190(12):6173-9. doi: 10.4049/jimmunol.1202573. Epub 2013 May 17.
IL-7 is a cytokine essential for T cell development and survival. However, the local function of IL-7 produced by thymic epithelial cells (TECs) is poorly understood. To address this question, we generated IL-7-floxed mice and crossed them with FoxN1 promoter-driven Cre (FoxN1-Cre) mice to establish knockout mice conditionally deficient for the expression of IL-7 by TECs. We found that αβ and γδ T cells were significantly reduced in the thymus of IL-7(f/f) FoxN1-Cre mice. Proportion of mature single-positive thymocytes was increased. In lymph nodes and the spleen, the numbers of T cells were partially restored in IL-7(f/f) FoxN1-Cre mice. In addition, γδ T cells were absent from the fetal thymus and epidermis of IL-7(f/f) FoxN1-Cre mice. Furthermore, TCRγδ(+) intraepithelial lymphocytes (IELs) were significantly decreased in the small intestines of IL-7(f/f) FoxN1-Cre mice. To evaluate the function of IL-7 produced in the intestine, we crossed the IL-7(f/f) mice with villin promoter-driven Cre (Vil-Cre) mice to obtain the mice deficient in IL-7 production from intestinal epithelial cells. We observed that αβ and γδ IELs of IL-7(f/f) Vil-Cre mice were comparable to control mice. Collectively, our results suggest that TEC-derived IL-7 plays a major role in proliferation, survival, and maturation of thymocytes and is indispensable for γδ T cell development. This study also demonstrates that IL-7 produced in the thymus is essential for the development of γδ IELs and indicates the thymic origin of γδ IELs.
IL-7 是一种对 T 细胞发育和存活至关重要的细胞因子。然而，胸腺上皮细胞（TEC）产生的 IL-7 的局部功能还知之甚少。为了解决这个问题，我们生成了 IL-7 基因敲除的小鼠，并与 FoxN1 启动子驱动的 Cre（FoxN1-Cre）小鼠杂交，以建立 TEC 中 IL-7 表达条件性缺失的敲除小鼠。我们发现，αβ 和 γδ T 细胞在 IL-7(f/f) FoxN1-Cre 小鼠的胸腺中显著减少。成熟的单阳性胸腺细胞比例增加。在淋巴结和脾脏中，IL-7(f/f) FoxN1-Cre 小鼠的 T 细胞数量部分恢复。此外，IL-7(f/f) FoxN1-Cre 小鼠的胎儿胸腺和表皮中没有 γδ T 细胞。此外，TCRγδ(+) 上皮内淋巴细胞（IEL）在 IL-7(f/f) FoxN1-Cre 小鼠的小肠中显著减少。为了评估肠道中产生的 IL-7 的功能，我们将 IL-7(f/f) 小鼠与绒毛蛋白启动子驱动的 Cre（Vil-Cre）小鼠杂交，以获得肠道上皮细胞中缺乏 IL-7 产生的小鼠。我们观察到，IL-7(f/f) Vil-Cre 小鼠的 αβ 和 γδ IEL 与对照小鼠相当。总之，我们的结果表明，TEC 衍生的 IL-7 在胸腺细胞的增殖、存活和成熟中发挥主要作用，并且对于 γδ T 细胞的发育是不可或缺的。本研究还表明，胸腺中产生的 IL-7 对于 γδ IEL 的发育是必需的，并表明 γδ IEL 来源于胸腺。
