Department of Biological Sciences, Institute of Molecular Biology and Genetics, and Research Center for Functional Cellulomics, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-742, Korea.
J Biol Chem. 2010 Jan 22;285(4):2340-50. doi: 10.1074/jbc.M109.026997. Epub 2009 Nov 12.
The SWI/SNF chromatin-remodeling complex has been implicated in the activation and proliferation of T cells. After T cell receptor signaling, the SWI/SNF complex rapidly associates with chromatin and controls gene expression in T cells. However, the process by which the SWI/SNF complex regulates peripheral T cell activation has not been elucidated. In this study, we show that the SWI/SNF complex regulates cytokine production and proliferation of T cells. During T cell activation, the SWI/SNF complex is recruited to the promoter of the transcription factor AP-1, and it increases the expression of AP-1. Increased expression of the SWI/SNF complex resulted in enhanced AP-1 activity, cytokine production, and proliferation of peripheral T cells, whereas knockdown of the SWI/SNF complex expression impaired the AP-1 expression and reduced the activation and proliferation of T cells. Moreover, mice that constitutively expressed the SWI/SNF complex in T cells were much more susceptible to experimentally induced autoimmune encephalomyelitis than the normal mice were. These results suggest that the SWI/SNF complex plays a critical role during T cell activation and subsequent immune responses.
SWI/SNF 染色质重塑复合物与 T 细胞的激活和增殖有关。在 T 细胞受体信号转导后，SWI/SNF 复合物迅速与染色质结合，并控制 T 细胞中的基因表达。然而，SWI/SNF 复合物调节外周 T 细胞激活的过程尚未阐明。在这项研究中，我们表明 SWI/SNF 复合物调节细胞因子的产生和 T 细胞的增殖。在 T 细胞激活期间，SWI/SNF 复合物被募集到转录因子 AP-1 的启动子，并且它增加了 AP-1 的表达。SWI/SNF 复合物表达的增加导致 AP-1 活性、细胞因子产生和外周 T 细胞的增殖增强，而 SWI/SNF 复合物表达的敲低则损害了 AP-1 的表达并减少了 T 细胞的激活和增殖。此外，在 T 细胞中组成性表达 SWI/SNF 复合物的小鼠比正常小鼠更容易发生实验性自身免疫性脑脊髓炎。这些结果表明，SWI/SNF 复合物在 T 细胞激活和随后的免疫反应中起着关键作用。
