Shi Yufeng, Feng Yan, Kang Jiuhong, Liu Chang, Li Zhenxin, Li Dangsheng, Cao Wei, Qiu Ju, Guo Zhengliang, Bi Enguang, Zang Lei, Lu Chuanzhen, Zhang Jingwu Z, Pei Gang
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Nat Immunol. 2007 Aug;8(8):817-24. doi: 10.1038/ni1489. Epub 2007 Jul 8.
CD4+ T cells are important in adaptive immunity, but their dysregulation can cause autoimmunity. Here we demonstrate that the multifunctional adaptor protein beta-arrestin 1 positively regulated naive and activated CD4+ T cell survival. We found enhanced expression of the proto-oncogene Bcl2 through beta-arrestin 1-dependent regulation of acetylation of histone H4 at the Bcl2 promoter. Mice deficient in the gene encoding beta-arrestin 1 (Arrb1) were much more resistant to experimental autoimmune encephalomyelitis, whereas overexpression of Arrb1 increased susceptibility to this disease. CD4+ T cells from patients with multiple sclerosis had much higher Arrb1 expression, and 'knockdown' of Arrb1 by RNA-mediated interference in those cells increased apoptosis induced by cytokine withdrawal. Our data demonstrate that beta-arrestin 1 is critical for CD4+ T cell survival and is a factor in susceptibility to autoimmunity.
CD4 + T细胞在适应性免疫中很重要，但其失调会导致自身免疫。在此我们证明多功能衔接蛋白β - 抑制蛋白1正向调节初始和活化的CD4 + T细胞存活。我们发现通过β - 抑制蛋白1依赖的Bcl2启动子上组蛋白H4乙酰化调节，原癌基因Bcl2的表达增强。编码β - 抑制蛋白1（Arrb1）的基因缺陷小鼠对实验性自身免疫性脑脊髓炎具有更强的抵抗力，而Arrb1的过表达增加了对该疾病的易感性。来自多发性硬化症患者的CD4 + T细胞具有更高的Arrb1表达，并且通过RNA介导的干扰在这些细胞中“敲低”Arrb1会增加细胞因子撤去诱导的细胞凋亡。我们的数据表明β - 抑制蛋白1对CD4 + T细胞存活至关重要，并且是自身免疫易感性的一个因素。
