生物谷报道：在7月8日在线出版的《自然—免疫学》期刊上，一篇论文揭示了T淋巴细胞如何生存下来并导致数种自体免疫性疾病，如多发性硬化症等。
通过对多发性硬化症模式小鼠的研究，Gang Pei和同事研究了一种名为beta-arrestin1的蛋白质，这种蛋白质是所有细胞中的基因表达调控因子。Pei的研究小组报告说，beta-arrestin1帮助促进了T淋巴细胞的生存，而T淋巴细胞能增加炎症的持续时间。缺失beta-arrestin1，T淋巴细胞存活所必要的一种关键因子就不能产出。同样地，缺少beta-arrestin1的T淋巴细胞不会活得很好，而且多发性硬化症模式小鼠大脑中的炎症减少了。
新研究揭示了beta-arrestin1在延长与自体免疫疾病相关的进攻性T淋巴细胞的生存机会中的作用，从而提供了一种减少这类疾病的潜在靶标。然而，阻断beta-arrestin1的功能是否有助于多发性硬化症患者呢？这还需要进一步的研究。（科学时报）
原始出处:
Nature Immunology
Published online: 8 July 2007 | doi:10.1038/ni1489
Critical regulation of CD4+ T cell survival and autoimmunity by -arrestin 1
Yufeng Shi1, Yan Feng2, Jiuhong Kang1, Chang Liu1, Zhenxin Li3, Dangsheng Li4, Wei Cao2, Ju Qiu2, Zhengliang Guo5, Enguang Bi1, Lei Zang1, Chuanzhen Lu3, Jingwu Z Zhang2,5,6 & Gang Pei1
Abstract
CD4+ T cells are important in adaptive immunity, but their dysregulation can cause autoimmunity. Here we demonstrate that the multifunctional adaptor protein -arrestin 1 positively regulated naive and activated CD4+ T cell survival. We found enhanced expression of the proto-oncogene Bcl2 through -arrestin 1–dependent regulation of acetylation of histone H4 at the Bcl2 promoter. Mice deficient in the gene encoding -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 -arrestin 1 is critical for CD4+ T cell survival and is a factor in susceptibility to autoimmunity.
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.
Joint Immunology Laboratory of Institute of Health Sciences and Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
Institute of Neurology, Huashan Hospital, Shanghai Medical College of Fudan University, Shanghai 200040, China.
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Department of Neurology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.
E-Institutes of Shanghai Universities, Shanghai 200240, China.
Correspondence to: Gang Pei1 e-mail: gpei@sibs.ac.cn
Correspondence to: Jingwu Z Zhang2,5,6 e-mail: jwzang@sibs.ac.cn
