英國科研人員最近確認(rèn),，E4bp4基因是促使造血干細(xì)胞轉(zhuǎn)變?yōu)樽匀粴?xì)胞（NK細(xì)胞）的主宰基因,。該發(fā)現(xiàn)有助于幫助科學(xué)家找到刺激NK細(xì)胞生成的方法,，從而研究出更有效的癌癥治療新法。該研究成果刊登在最近出版的《自然·免疫學(xué)》雜志上,。
此項(xiàng)研究由英國倫敦帝國學(xué)院,、倫敦大學(xué)和英國醫(yī)學(xué)研究理事會(huì)國家醫(yī)學(xué)研究所的研究人員共同完成?？蒲行〗M在研究一種罕見,、致命的兒童白血病時(shí)，發(fā)現(xiàn)了E4bp4基因?qū)K細(xì)胞的重要作用,。為證實(shí)該發(fā)現(xiàn),，研究人員建立了世界上第一個(gè)完全缺乏NK細(xì)胞的動(dòng)物模型。他們剔除了小鼠體內(nèi)的E4bp4基因,，而沒有該基因,，小鼠體內(nèi)就無法生成NK細(xì)胞，其他所有的血液細(xì)胞和免疫細(xì)胞則完好無損,。
NK細(xì)胞是人體免疫系統(tǒng)的一個(gè)主要組成部分,，和其他類型的血液細(xì)胞一樣，由人體骨髓間充質(zhì)造血干細(xì)胞分化而來,。這種細(xì)胞具有自然殺傷活性,，能夠分泌多種細(xì)胞因子，在機(jī)體抗病毒感染,、免疫監(jiān)視中起重要作用,，可快速構(gòu)筑防線對(duì)抗腫瘤、病毒和細(xì)菌感染,。目前,，從血液中分離NK細(xì)胞后注入患者體內(nèi)是一種時(shí)常被應(yīng)用的癌癥療法，但由于患者與獻(xiàn)血者的細(xì)胞差異,，該種治療效果有限,，有時(shí)會(huì)產(chǎn)生排異現(xiàn)象。研究人員希望該發(fā)現(xiàn)能夠幫助科學(xué)家研究出新藥,，通過藥物治療,，刺激E4bp4基因表達(dá)，增加患者血液干細(xì)胞分化成NK細(xì)胞的數(shù)量,，以增強(qiáng)人體抗癌的能力,。
自20世紀(jì)70年代NK細(xì)胞被發(fā)現(xiàn)以來，一些科學(xué)家就懷疑,，該種細(xì)胞不僅與抗腫瘤,、抗病毒感染和免疫調(diào)節(jié)有關(guān)，而且在某些情況下會(huì)參與超敏反應(yīng)和誘發(fā)自身免疫性疾病,，因此,，NK細(xì)胞功能障礙與許多嚴(yán)重疾病有關(guān)。對(duì)此，該項(xiàng)研究的領(lǐng)導(dǎo)者,、倫敦帝國學(xué)院生命科學(xué)系的休·布萊迪博士指出,，他們創(chuàng)立的小鼠模型不僅證明了關(guān)于E4bp4基因功能的假設(shè)，還可用來觀察NK細(xì)胞功能障礙與多種病癥,，如自身免疫失調(diào),、發(fā)炎、病毒感染,、女性不孕及器官移植排斥等的關(guān)聯(lián),。對(duì)于NK細(xì)胞是否總是“好孩子”，某些情況下它們對(duì)人體是否也會(huì)弊大于利的問題,，將會(huì)有明確的答案,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Immunology 13 September 2009 | doi:10.1038/ni.1787
The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development
Duncan M Gascoyne1, Elaine Long1, Henrique Veiga-Fernandes2,6, Jasper de Boer1, Owen Williams1, Benedict Seddon3, Mark Coles4, Dimitris Kioussis2 & Hugh J M Brady1,5
Abstract
Natural killer (NK) cells are a subset of lymphocytes crucial for innate immunity and modification of adaptive immune responses. In contrast to commitment to the T cell or B cell lineage, little is known about NK cell lineage commitment. Here we show that the basic leucine zipper (bZIP) transcription factor E4BP4 (also called NFIL3) is essential for generation of the NK cell lineage. E4BP4-deficient mice (Nfil3-/–; called 'E4bp4-/–' here) had B cells, T cells and NKT cells but specifically lack NK cells and showed severely impaired NK cell–mediated cytotoxicity. Overexpression of E4bp4 was sufficient to increase NK cell production from hematopoietic progenitor cells. E4BP4 acted in a cell-intrinsic manner 'downstream' of the interleukin 15 receptor (IL-15R) and through the transcription factor Id2. E4bp4-/- mice may provide a model for definitive analysis of the contribution of NK cells to immune responses and pathologies.
1 Molecular Haematology and Cancer Biology Unit, University College London Institute of Child Health and Great Ormond Street Hospital for Children, London, UK.
2 Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, Mill Hill, London, UK.
3 Division of Immune Cell Biology, Medical Research Council National Institute for Medical Research, Mill Hill, London, UK.
4 Centre for Immunology and Infection, Department of Biology and Hull York Medical School, University of York, UK.
5 Immunology and Infection Section, Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College, London, UK.
6 Present address: Immunobiology Unit, Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Lisboa, Portugal.
