Villarino Alejandro V, Tato Cristina M, Stumhofer Jason S, Yao Zhengju, Cui Yongzhi K, Hennighausen Lothar, O'Shea John J, Hunter Christopher A
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA.
J Exp Med. 2007 Jan 22;204(1):65-71. doi: 10.1084/jem.20061198. Epub 2007 Jan 16.
Although required for many fundamental immune processes, ranging from self-tolerance to pathogen immunity, interleukin (IL)-2 production is transient, and the mechanisms underlying this brevity remain unclear. These studies reveal that helper T cell IL-2 production is limited by a classic negative feedback loop that functions autonomously or in collaboration with other common gamma chain (IL-4 and IL-7) and IL-6/IL-12 family cytokines (IL-12 and IL-27). Consistent with this model for cytokine-dependent regulation, they also demonstrate that the inhibitory effect can be mediated by several signal transducer and activator of transcription (STAT) family transcription factors, namely STAT5, STAT4, and STAT6. Collectively, these findings establish that IL-2 production is limited by a network of autocrine and paracrine signals that are readily available during acute inflammatory responses and, thus, provide a cellular and molecular basis for its transient pattern of expression.
尽管白细胞介素（IL）-2的产生对于许多基本免疫过程都是必需的，从自身耐受性到病原体免疫，但IL-2的产生是短暂的，而这种短暂性背后的机制仍不清楚。这些研究表明，辅助性T细胞IL-2的产生受到一个经典负反馈回路的限制，该回路可自主发挥作用，或与其他共同γ链（IL-4和IL-7）以及IL-6/IL-12家族细胞因子（IL-12和IL-27）协同发挥作用。与这种细胞因子依赖性调节模型一致，他们还证明这种抑制作用可由几种信号转导和转录激活因子（STAT）家族转录因子介导，即STAT5、STAT4和STAT6。总体而言，这些发现表明，IL-2的产生受到急性炎症反应期间随时可用的自分泌和旁分泌信号网络的限制，因此为其短暂的表达模式提供了细胞和分子基础。
