生物谷綜合： 追求長(zhǎng)壽的人們一定不會(huì)想到，身體里的免疫細(xì)胞要是異常地“高壽”，就可能導(dǎo)致免疫系統(tǒng)攻擊自身器官的“內(nèi)亂”發(fā)生,。最近，上?？茖W(xué)家發(fā)現(xiàn)了一種名叫β-arrestin1的蛋白(簡(jiǎn)稱β蛋白)在生命體內(nèi)誘導(dǎo)著這樣一場(chǎng)混亂,。今天凌晨出版的國(guó)際重要學(xué)術(shù)期刊《自然·免疫學(xué)》雜志刊登了這一最新成果。
按照正常的生命進(jìn)程,，當(dāng)人體的先天免疫系統(tǒng)抵御不了病毒,、細(xì)菌等“外敵”時(shí)，會(huì)向CD4＋T細(xì)胞發(fā)出求救信號(hào),，讓它趕緊征召各類獲得性免疫細(xì)胞投入“保衛(wèi)戰(zhàn)”,。戰(zhàn)斗結(jié)束后，CD4＋T細(xì)胞就會(huì)自動(dòng)“卸任”———在外周免疫系統(tǒng)中凋亡,。
中科院上海生科院生物化學(xué)和細(xì)胞生物學(xué)研究所裴鋼院士研究組和中科院上海生科院/上海交大醫(yī)學(xué)院健康科學(xué)研究所臧敬五教授研究組經(jīng)過(guò)長(zhǎng)期合作發(fā)現(xiàn)，當(dāng)大量β蛋白出現(xiàn)在CD4＋T細(xì)胞中,，這種細(xì)胞就像吃了長(zhǎng)生不老藥一樣,，突然長(zhǎng)壽起來(lái)———即使在完成任務(wù)后，也不凋亡,。盡管大多數(shù)的CD4＋T細(xì)胞會(huì)安分地頤養(yǎng)天年,，但其中能攻擊自身器官的“野心家”則得到了蠢蠢欲動(dòng)的機(jī)會(huì)。一旦受到環(huán)境影響,，或基因變異,，這些“野心家”就會(huì)鉆起防范機(jī)制出現(xiàn)的“漏洞”，逃離監(jiān)管，征召懵懵懂懂的免疫細(xì)胞,，攻擊自身器官,，造成自身免疫疾病，如多發(fā)性硬化并紅斑狼瘡等,。
“我們已為這個(gè)成果申請(qǐng)了專利,。”裴鋼院士告訴記者，這個(gè)研究揭示出生物體內(nèi)調(diào)節(jié)CD4＋T細(xì)胞凋亡和自身免疫的新機(jī)制,，并提示β蛋白有可能成為研發(fā)自身免疫治療藥物的新靶點(diǎn),。
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.
