Role of NF-kB recruited SWI/SNF chromatin remodeling complexes in inducible gene expression in T cells

免疫系统由一组细胞类型组成，包括T细胞，它们能够识别异物并将其从体内清除。T细胞被外来抗原激活，并通过产生包括细胞因子在内的一系列可溶性因子来做出反应，这些因子充当细胞之间的通信者。这些因子的正确表达对免疫系统的维持和功能至关重要，因此受到严格的调控。编码这些因子的基因通常保持在不活跃的状态，但在需要时会迅速启动。在细胞内，基因或DNA被包裹在一种名为染色质的复杂蛋白质结构中，该结构在调节基因表达方面发挥着重要作用。染色质形成了活跃基因表达的障碍，必须先克服这一障碍，然后基因才能启动。细胞内的蛋白质复合体能够改变或重塑染色质结构，使其从“不活跃”变为“活跃”状态。我们正在研究这些染色质重塑复合体中的一个，以确定它能够启动哪些基因，以及它如何针对这些特定的基因。T细胞内异常的基因表达导致一系列疾病，包括某些白血病和炎症性疾病，如哮喘和类风湿性关节炎。了解T细胞中涉及开启特定基因的事件和蛋白质复合体，将有可能识别可以作为靶点的分子，以努力控制这些疾病状态下的不适当基因表达。

The immune system consists of a group of cell types, including T cells, which are capable of recognising foreign agents and eradicating them from the body. T cells are activated by foreign antigen and respond by producing an array of soluble factors including cytokines, which act as communicators between cells. The correct expression of these factors is critical for the maintenance and function of the immune system, and is therefore tightly regulated. The genes encoding these factors are generally maintained in an 'inactive' state but are switched on rapidly when required. Within the cell, genes or DNA are found wrapped up in a complex protein structure called chromatin which plays an important role in regulating gene expression. Chromatin forms a barrier to active gene expression which must be overcome before the gene can be switched on. There are protein complexes within the cell that are able to alter or remodel chromatin structure from an 'inactive' to an 'active' state. We are investigating one of these chromatin remodeling complexes to determine which genes it is able to switch on and how it targets these particular genes. Aberrant gene expression within T cells contributes to a range of diseases including certain leukemias and inflammatory conditions such as asthma and rheumatoid arthritis. Understanding the events and protein complexes involved in switching on specific genes in T cells will potentially identify molecules which can be targeted in an effort to control inappropriate gene expression in these disease states.