Gene transcription in activated T cells: a model of chromatin remodeling.

免疫系统的细胞通过启动大量蛋白质的生产来应对感染或其他有害物质对身体的入侵，这些蛋白质对精心安排的免疫反应至关重要。其中一些蛋白质被称为细胞因子，由细胞分泌，充当细胞间信使，影响免疫反应所需的其他细胞的功能。开启这些细胞因子的产生需要产生它们的基因来解释细胞所暴露的复杂信号模式。这些复杂的信号模式在细胞核中由位于DNA基因旁边的分子开关来解释。这些蛋白质的错误产生与免疫疾病有关，如自身免疫、过敏和白血病。基因被安置在细胞核中，被包装成一种被称为染色质的结构。当基因不产生蛋白质时，它被紧密地包裹在染色质中，但当它被激活产生蛋白质时，这种包装被改变，使基因能够看到细胞接收到的信号并产生蛋白质。我们已经在细胞核中发现了一种蛋白质，这种蛋白质对某些细胞因子基因看到细胞核中接收到的信号至关重要。通过研究这种蛋白（称为c-Rel）在免疫细胞染色质重组中的作用，我们希望更好地定义免疫反应中适当基因激活所需的步骤。反过来，这一知识将导致识别新的治疗靶点来控制免疫反应

Cells of the immune system respond to invasion of the body by infectious or other damaging agents by switching on the production of a large array of proteins that are critical for an orchestrated immune response. Some of these proteins, referred to as cytokines, are secreted by the cells and act as intercellular messengers to affect the function of other cells need for an immune response. Switching on the production of these cytokines requires the genes that produce them to interpret the complex signaling pattern to which the cell has been exposed. These complex signaling patterns are interpreted in the nucleus by molecular switches that lie beside the genes in the DNA. The incorrect production of these proteins is involved in immune diseases such as autoimmunity, allergy and leukemia. Genes are housed in the nucleus of the cell, packaged into a structure known as chromatin. When the gene is not producing protein it is tightly packaged in chromatin but when it is activated to produce protein this packaging is altered to allow the gene to see the signals being received by the cell and produce protein. We have identified a protein within the nucleus that is critical in allowing certain cytokine genes to see the signals being received in the nucleus. By investigating the role of this protein (called c-Rel) in chromatin reorganization in immune cells, we hope to better define the steps required for appropriate gene activation in an immune response. This knowledge, in turn, will lead to the identification of novel therapeutic targets to control immune responses