鼻塞,、打噴嚏,、瘙癢……越來越多的現(xiàn)代人正被過敏反應(yīng)困擾。過敏看似小病,，嚴(yán)重時 卻可給患者帶來生命危險,。英國和瑞士科學(xué)家通過研究發(fā)現(xiàn)了過敏元兇——基因缺陷，并希望借此開發(fā)醫(yī)治花粉過敏等過敏癥的新療法,，為患者帶去福音,。
關(guān)鍵基因
過敏癥狀來自免疫系統(tǒng)錯誤識別如沙礫、花粉,、花生以及貓毛等過敏原,，將其視為威脅，并指揮人體產(chǎn)生組胺抗體,，對人體的一些正常細(xì)胞和組織發(fā)起攻擊,，并引發(fā)諸如瘙癢、哮喘及打噴嚏之類癥狀,。在正常人體內(nèi),，能夠產(chǎn)生一種“調(diào)節(jié)性Ｔ細(xì)胞”物質(zhì)，控制免疫系統(tǒng)的過度反應(yīng),。但在過敏癥患者體內(nèi),，這種細(xì)胞卻無法正常生成。
倫敦帝國學(xué)院和瑞士變應(yīng)性疾病和哮喘研究所的科學(xué)家在２７日出版的美國《公共科學(xué)圖書館·生物學(xué)》雜志上發(fā)表文章,，稱找到了調(diào)節(jié)性Ｔ細(xì)胞無法生成的原因,。
研究者通過分析調(diào)節(jié)性Ｔ細(xì)胞生成機制及它們和相關(guān)基因的聯(lián)系，發(fā)現(xiàn)一種ＧＡＴＡ－３基因,。它能夠通過抑制另一種基因ＦＯＸＰ３發(fā)揮作用,，阻礙調(diào)節(jié)性Ｔ細(xì)胞的生成，從而使免疫系統(tǒng)對外界異物產(chǎn)生過度反應(yīng),，引發(fā)過敏癥狀,。
科學(xué)家在老鼠身上實驗后發(fā)現(xiàn)，當(dāng)老鼠體內(nèi)所有的Ｔ細(xì)胞都根據(jù)ＧＡＴＡ－３基因表達(dá)時,，老鼠在復(fù)制調(diào)節(jié)性Ｔ細(xì)胞方面存在嚴(yán)重缺陷,。
基因失衡
調(diào)節(jié)性Ｔ細(xì)胞在人體免疫系統(tǒng)中扮演重要角色。它們能夠抑制“親過敏”的Ｔｈ２細(xì)胞生成,，避免免疫系統(tǒng)對異物產(chǎn)生不必要的反應(yīng),。
科學(xué)家在研究調(diào)節(jié)性Ｔ細(xì)胞生成機制時發(fā)現(xiàn)，這種細(xì)胞的生成是ＧＡＴＡ－３與ＦＯＸＰ３基因“斗爭”的結(jié)果,，如果“邪惡”的ＧＡＴＡ－３獲勝,，人體免疫系統(tǒng)就會出現(xiàn)故障。
主持研究的倫敦帝國學(xué)院全國心肺研究所卡斯滕·施密特－韋伯博士介紹,，ＦＯＸＰ３可以促使生成調(diào)節(jié)性Ｔ細(xì)胞,，但是它們卻容易受到ＧＡＴＡ－３的抑制,。如果ＦＯＸＰ３占主導(dǎo)地位，人體就能正常生成調(diào)節(jié)性Ｔ細(xì)胞,，控制免疫系統(tǒng),；但一旦足量的ＧＡＴＡ－３限制了ＦＯＸＰ３，調(diào)節(jié)性Ｔ細(xì)胞就無法正常生成,，Ｔｈ２細(xì)胞就會大量繁殖,，使人體產(chǎn)生過敏反應(yīng)。
韋伯在研究報告中說,，目前還不知道“戰(zhàn)斗”的勝負(fù)如何決定,，但這可能與上述兩種基因各自的位置有關(guān)，同時,，“我們枯燥的,、西方人的生活方式也與它有關(guān)”。
對癥治療
關(guān)于這一發(fā)現(xiàn)的應(yīng)用前景,，韋伯說：“這項發(fā)現(xiàn)能幫助我們理解正常人如何接受過敏原,，以及我們應(yīng)該如何在免疫系統(tǒng)中重新引入接納機制來治療過敏癥。”
根據(jù)已有研究,，過敏癥可能由基因和外界環(huán)境兩方面引起,，但是遺傳性的過敏癥大部分與基因關(guān)系最為密切。如果父母患有過敏癥,，孩子通常更容易患病,，研究者認(rèn)為這可能就是因為孩子遺傳的ＧＡＴＡ－３出現(xiàn)異常，而并不是外界環(huán)境中某種過敏原所致,。
當(dāng)然,，基因缺陷并非目前增多的過敏癥的唯一原因，導(dǎo)致過敏頻發(fā)的環(huán)境因素包括童年時期感染傳染性疾病,、環(huán)境污染,、過敏原含量以及飲食變化等。
研究者希望這項發(fā)現(xiàn)最終可以催生對花粉過敏和其他一些過敏的更有效療法,，配合現(xiàn)存的免疫療法,，有效控制正常過敏反應(yīng)發(fā)生病變,。（胡曉白）
原始出處：
PLoS Biology
Received: March 16, 2007; Accepted: November 6, 2007; Published: December 27, 2007
GATA3-Driven Th2 Responses Inhibit TGF-β1–Induced FOXP3 Expression and the Formation of Regulatory T Cells
Pierre-Yves Mantel1, Harmjan Kuipers2, Onur Boyman3, Claudio Rhyner1, Nadia Ouaked1, Beate Rückert1, Christian Karagiannidis1, Bart N. Lambrecht2, Rudolf W. Hendriks2,4, Reto Crameri1, Cezmi A. Akdis1, Kurt Blaser1, Carsten B. Schmidt-Weber1,5*
1 Swiss Institute of Allergy and Asthma Research Davos (SIAF), Davos-Platz, Switzerland, 2 Department of Pulmonary Medicine, Erasmus Medical College, Rotterdam, The Netherlands, 3 Division of Immunology and Allergy, University Hospital of Lausanne (CHUV), Lausanne, Switzerland, 4 Department of Immunology, Erasmus Medical College, Rotterdam, The Netherlands, 5 Department of Allergy and Clinical Immunology, Imperial College London, London, United Kingdom
Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-β–mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.
Figure 1.Th2 Cells Cannot Induce FOXP3 Expression
全文鏈接：
http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0050329
