10月30日,，免疫學(xué)專業(yè)期刊《免疫學(xué)雜志》（Journal of Immunology）發(fā)表了中國(guó)科學(xué)院上海生命科學(xué)研究院生物化學(xué)與細(xì)胞生物學(xué)研究所孫兵研究組最新研究成果：轉(zhuǎn)錄調(diào)控因子Dec2在Th2細(xì)胞分化中的調(diào)控機(jī)制,。這一研究成果進(jìn)一步揭示了Th2細(xì)胞分化的調(diào)控網(wǎng)絡(luò),，并有助于了解Th2細(xì)胞介導(dǎo)的過(guò)敏性疾病的發(fā)病機(jī)制,。
過(guò)敏性疾病如過(guò)敏性哮喘主要由Th2細(xì)胞所介導(dǎo),。當(dāng)機(jī)體幼稚Th細(xì)胞被抗原遞呈細(xì)胞激活后,，經(jīng)過(guò)克隆增殖與細(xì)胞分化,，形成不同的細(xì)胞亞型如Th1,，Th2,，Th17和Treg等。不同的細(xì)胞亞型介導(dǎo)不同的疾病,，其中Th2細(xì)胞分泌大量的白介素4,，5和13，在抗寄生蟲以及過(guò)敏反應(yīng)中起到重要的作用,。然而Th2細(xì)胞分化的精確調(diào)控仍不清楚,，深入研究Th2細(xì)胞分化的調(diào)控網(wǎng)絡(luò)，對(duì)包括哮喘在內(nèi)的過(guò)敏性疾病的治療和預(yù)防有重要意義,。
孫兵研究組的劉智多和李振虎博士發(fā)現(xiàn),，一個(gè)從屬于bHLH (basic helix-loop-helix) 超家族的轉(zhuǎn)錄因子Dec2， 在Th細(xì)胞朝向Th2方向分化的過(guò)程中被逐漸地誘導(dǎo)表達(dá),，而且這一趨勢(shì)在Th2細(xì)胞分化的后期顯得尤為明顯,。在Th2細(xì)胞誘導(dǎo)的條件下，即在IL-4信號(hào)開(kāi)放的條件下,，Dec2能夠強(qiáng)力促進(jìn)Th2細(xì)胞的分化,。相反，如果用RNA干擾的方法下調(diào)細(xì)胞內(nèi)的Dec2的表達(dá)水平,，Th2細(xì)胞分化的進(jìn)程就會(huì)受到抑制,。另外，他們?cè)谟肙VA誘導(dǎo)的小鼠過(guò)敏性哮喘模型中發(fā)現(xiàn),，相比于對(duì)照小鼠Dec2轉(zhuǎn)基因小鼠里檢測(cè)到了更強(qiáng)的Th2免疫反應(yīng),。此項(xiàng)工作揭示Dec2是通過(guò)上調(diào)IL-2R的α亞基,，也就是CD25的表達(dá)水平，來(lái)增強(qiáng)IL-2信號(hào)通路,，進(jìn)而更好地促進(jìn)Th2的分化,。該研究不僅發(fā)現(xiàn)了一個(gè)新的Th2細(xì)胞分化調(diào)控機(jī)制，闡明了IL-2和IL-4在Th2的分化中發(fā)揮了同等的作用,，還為過(guò)敏性疾病的治療提供了一個(gè)新的藥物靶點(diǎn),。
此項(xiàng)研究成果得到科技部973、國(guó)家自然科學(xué)基金,、上海市科學(xué)技術(shù)委員會(huì)和中國(guó)科學(xué)院的資金資助,。浙江大學(xué)項(xiàng)春生教授在用DNA芯片技術(shù)篩選Dec2基因的研究中，做出了重要貢獻(xiàn),。（生物谷Bioon.com）
生物谷推薦原始出處：
The Journal of Immunology, 2009, 183, 6320 -6329 doi:10.4049/jimmunol.0900975
Dec2 Promotes Th2 Cell Differentiation by Enhancing IL-2R Signaling1
Zhiduo Liu,2* Zhenhu Li,2* Kairui Mao,* Jia Zou,* Yuan Wang,* Zhiyun Tao,* Guomei Lin,* Lin Tian,* Yongyong Ji,* Xiaodong Wu,* Xueliang Zhu,* Shuhui Sun, Weiguang Chen, Charlie Xiang,3 and Bing Sun3*
*Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Institute Pasteur of Shanghai, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Fudan University School of Medicine, Shanghai, China; and State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Th cell differentiation is precisely regulated by thousands of genes at different stages. In the present study, we demonstrate that Dec2, a transcription factor belonging to the bHLH (basic helix-loop-helix) superfamily, is progressively induced during the course of Th2 differentiation, especially at the late stage. The up-regulated Dec2 can strongly promote Th2 development under Th2-inducing conditions, as evidenced by retrovirus-mediated gene transfer or transgenic manipulation. In addition, an enhancement of Th2 responses is also detectable in Dec2 transgenic mice in vivo. Conversely, RNA interference-mediated suppression of endogenous Dec2 could attenuate Th2 differentiation. Finally, we show that the enhanced Th2 development is at least in part due to substantial up-regulation of CD25 expression elicited by Dec2, thereby resulting in hyperresponsiveness to IL-2 stimulation.
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1 This work was supported by Grants from the National Natural Science Foundation of China (30530700, 30623003, 30600568, 30721065, 90713044, 30600308, 30801011, 30870126) and the CAS project (KSCX1-YW-R-43), a grant from the SIBS project (2007KIP301), grants from the Ministry of Science and Technology (2006CB504300, 2007CB512404, 2006AA02A247, 20072714), grants from the Technology Commission of Shanghai Municipality (88014199, 07DZ22916, 07XD14033, 064319034, 08431903004, 2008ZX10206, 08DZ2291703), the EU project (FP6-2005-SSP-5-B, SP5B-CT-2006-044161), the National Basic Research Program of China (973 Program, No. 2007CB513001) and a grant from the E-institutes of Shanghai Universities Immunology Division.
2 Z. Liu and Z. Li contributed equally to this study.
3 Address correspondence and reprint requests to Dr. Bing Sun, Laboratory of Molecular Immunology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, China or Dr. Charlie Xiang, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
4 Abbreviations used in this paper: bHLH, basic helix-loop-helix; hCD4, human CD4; Treg, regulatory T cell; siRNA, short-interfering RNA; MFI, mean fluorescence intensity; RNAi, RNA interference; iTreg, induced regulatory T cell; MSCV, mouse stem cell virus.
5 The online version of this article contains supplementary material.
