Institute of Immunology, Charité Campus Benjamin Franklin, Berlin, Germany.
Eur J Immunol. 2010 Sep;40(9):2391-400. doi: 10.1002/eji.201040441.
IL-7 is a major regulator of lymphocyte homeostasis; however, little is known about the mechanisms that regulate IL-7 production. To study Il7 gene regulation in vivo, we generated a novel IL-7-reporter mouse, which allows the non-invasive quantification of Il7 gene activity in live mice and, additionally, the simultaneous activation/inactivation of target genes in IL-7-producing cells. With these IL-7-reporter mice, we identify thymus, skin and intestine as major sources of IL-7 in vivo. Importantly, we show that IFN-gamma and the commensal microflora promote steady-state IL-7 production in the intestine. Furthermore, we demonstrate that the blockade of IFN-gamma signaling in intestinal epithelial cells strongly reduces their IFN-gamma-driven IL-7 production. In summary, our data suggest a feedback loop in which commensal bacteria drive IFN-gamma production by lymphocytes, which in turn promotes epithelial cell IL-7 production and the survival of IL-7-dependent lymphocytes.
IL-7 是调节淋巴细胞动态平衡的主要调控因子；然而，关于调节 IL-7 产生的机制却知之甚少。为了研究体内 Il7 基因的调控，我们构建了一种新型的 IL-7 报告小鼠，该小鼠可在活体小鼠中对 Il7 基因活性进行非侵入性定量，并能同时激活/失活 IL-7 产生细胞中的靶基因。利用这些 IL-7 报告小鼠，我们确定了胸腺、皮肤和肠道是体内 IL-7 的主要来源。重要的是，我们发现 IFN-γ 和共生微生物促进了肠道中 IL-7 的稳态产生。此外，我们证明了阻断肠道上皮细胞中的 IFN-γ 信号通路可显著减少其由 IFN-γ 驱动的 IL-7 产生。总之，我们的数据表明，共生细菌通过淋巴细胞驱动 IFN-γ 产生，而 IFN-γ 反过来又促进了上皮细胞 IL-7 的产生和 IL-7 依赖性淋巴细胞的存活，形成了一个反馈回路。
