據(jù)“中央社”報(bào)道,，臺(tái)灣“中央研究院”分子生物研究所賴明宗研究團(tuán)隊(duì)，利用實(shí)驗(yàn)小鼠首次發(fā)現(xiàn)免疫控制分子Deltex1的全新功能,。
人體內(nèi)有眾多的免疫細(xì)胞,，其中T淋巴細(xì)胞(即T細(xì)胞)主導(dǎo)細(xì)胞免疫反應(yīng)，T細(xì)胞擔(dān)任的是指揮官角色,，快速辨識(shí)病毒并調(diào)度功能不同的免疫細(xì)胞,，與病原對(duì)抗。有關(guān)T細(xì)胞如何被啟動(dòng)活化,，研究相當(dāng)多,，但對(duì)于T細(xì)胞靜默的分子機(jī)制，科學(xué)家了解很少,。
賴明宗研究團(tuán)隊(duì)的研究清楚呈現(xiàn)Deltex1于人體免疫T細(xì)胞活化過(guò)程中,，扮演多種機(jī)制的修飾作用，對(duì)免疫研究學(xué)界有基礎(chǔ)性的重要解釋功用，受到國(guó)際矚目,。
研究團(tuán)隊(duì)是以先前在果蠅所發(fā)現(xiàn)的Deltex1分子為研究對(duì)象,，Deltex1在哺乳類(lèi)的功能一直不清楚，研究團(tuán)隊(duì)發(fā)現(xiàn),，Deltex1在T細(xì)胞靜默時(shí)會(huì)大量表現(xiàn),，用來(lái)抑制T細(xì)胞活化，如果將Deltex1轉(zhuǎn)殖基因表現(xiàn)在小鼠上,，則小鼠T細(xì)胞幾乎無(wú)法活化,。
研究團(tuán)隊(duì)也證實(shí)，如果將Deltex1基因從小鼠剔除,，T細(xì)胞會(huì)高度活化,，小鼠產(chǎn)生自體抗體，并出現(xiàn)多重器官發(fā)炎,，也就是說(shuō),，Deltex1是個(gè)全新了解T細(xì)胞是否即將啟動(dòng)的重要因子，并且Deltex1也是T細(xì)胞靜默訊息網(wǎng)絡(luò)重要的一個(gè)開(kāi)關(guān),。
“中研院”表示，對(duì)于T細(xì)胞為何靜默的深入了解,，將有助未來(lái)醫(yī)學(xué)界臨床運(yùn)用,。如能引導(dǎo)T細(xì)胞進(jìn)入靜默狀態(tài)，很可能可以預(yù)防器官移植排斥作用和治療自體免疫疾病,。反之,，掌握住如何喚醒靜默中的T細(xì)胞，將可以更有效對(duì)抗癌細(xì)胞或病原體感染,。（生物谷Bioon.com）
生物谷推薦原始出處：
Immunity, 09 July 2009 doi:10.1016/j.immuni.2009.04.017
Deltex1 Is a Target of the Transcription Factor NFAT that Promotes T Cell Anergy
Huey-Wen Hsiao1,2,4,Wen-Hsien Liu2,4,Chen-Jhe Wang2,Yu-Hsun Lo2,Yung-Hsuan Wu1,2,Si-Tse Jiang2andMing-Zong Lai1,2,3,,
1 Graduate Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 11221, Taiwan, ROC
2 Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, ROC
3 Graduate Institute of Immunology, National Taiwan University, Taipei 10002, Taiwan, ROC
The molecular process underlying Tcell anergy is incompletely understood. Deltex1 (DTX1) is a Notch target with unknown physiological function. Here we show that Dtx1 was a transcription target of nuclear factor of activated Tcells (NFAT) and participated in Tcell anergy. DTX1 protein was upregulated during Tcell anergy, and transgenic expression of Dtx1 attenuated Tcell activation. DTX1 inhibited Tcell activation by both E3-dependent and E3-independent mechanisms. In addition, DTX1 suppressed Tcell activation in the absence of its Notch-binding domain. Importantly, DTX1 regulated the expression of two anergy-associated molecules, growth arrest and DNA-damage-inducible 45 (Gadd45) and Cbl-b. DTX1 interacted with early growth response 2 (Egr-2) for optimum expression of Cbl-b. Furthermore, deficiency of DTX1 augmented Tcell activation, conferred resistance to anergy induction, enhanced autoantibody generation, and increased inflammation. DTX1 therefore represents a component downstream of calcium-NFAT signaling that regulates Tcell anergy.
