生物谷報(bào)道：在7月8日在線出版的《自然—免疫學(xué)》期刊上,，一篇論文揭示了T淋巴細(xì)胞如何生存下來并導(dǎo)致數(shù)種自體免疫性疾病,，如多發(fā)性硬化癥等。
通過對多發(fā)性硬化癥模式小鼠的研究,，Gang Pei和同事研究了一種名為beta-arrestin1的蛋白質(zhì),，這種蛋白質(zhì)是所有細(xì)胞中的基因表達(dá)調(diào)控因子。Pei的研究小組報(bào)告說,，beta-arrestin1幫助促進(jìn)了T淋巴細(xì)胞的生存,，而T淋巴細(xì)胞能增加炎癥的持續(xù)時(shí)間。缺失beta-arrestin1,，T淋巴細(xì)胞存活所必要的一種關(guān)鍵因子就不能產(chǎn)出,。同樣地，缺少beta-arrestin1的T淋巴細(xì)胞不會(huì)活得很好,，而且多發(fā)性硬化癥模式小鼠大腦中的炎癥減少了,。
新研究揭示了beta-arrestin1在延長與自體免疫疾病相關(guān)的進(jìn)攻性T淋巴細(xì)胞的生存機(jī)會(huì)中的作用,，從而提供了一種減少這類疾病的潛在靶標(biāo),。然而，阻斷beta-arrestin1的功能是否有助于多發(fā)性硬化癥患者呢,？這還需要進(jìn)一步的研究,。（科學(xué)時(shí)報(bào)）
原始出處:
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: [email protected]
Correspondence to: Jingwu Z Zhang2,5,6 e-mail: [email protected]
