曹雪涛院士连发Nature、Blood文章

　　

生物通报道，近期曹雪涛院士在《Nature Immunity》以及《Blood》上连发文章。

 

科学曹雪涛院士受邀在《Nature Immunity》上发表评述文章，New DNA-sensing pathway feeds RIG-I with RNA，为近期发表在Cell和Nature Immunity的热点免疫学文章进行评述。

 

免疫系统如何识别病毒入侵从而迅速产生干扰素、有效地触发天然抗病毒免疫防御功能进而清除病毒感染，是生命科学与医学研究中的重大科学问题。其中，寻找能够识别入侵细胞内病毒的分子并研究其作用机制更是前沿热点领域。近期有两篇来自美国和德国两个研究小组的研究论文几乎同时报道了一种新的识别DNA病毒并触发干扰素产生的分子机制，这两篇论文分别发表于国际一流学术杂志《细胞》和《自然—免疫学》。

 

据时报报道，机体抗御病毒感染的重要机制是有效识别入侵病毒的异源成分并迅速启动天然免疫以及随后的特异性免疫应答对病毒进行清除，但是，人们对于机体如何特异性感知病毒入侵和识别病毒特别是DNA病毒的分子机制，目前尚不清楚。因此，近年来众多科学家积极投身于发现和鉴定细胞内识别DNA病毒的新型蛋白分子，并分析其信号通路这个意义重大但竞争性激烈的课题研究之中。一旦免疫识别病毒的新机制研究有所突破，将为病毒及其他病原体感染的防治带来新的希望。

 

分别来自美国和德国的两个研究小组几乎同时发表了结果相似的两篇论文，报道了机体通过一种称为RNA多聚酶III的蛋白分子识别侵入细胞内的DNA病毒，然后以病毒DNA为模板，将病毒信息转录成一种特殊的双链RNA，再通过该特殊RNA被以往已经证明能够识别RNA病毒的RIG-I分子所识别，最终由RIG-I激活细胞的特定信号转导通路，诱导干扰素产生，从而抑制病毒等病原体复制。

 

为此，曹雪涛就有关机体如何识别DNA病毒以产生干扰素免疫应答的新机制进行了评论，并对免疫识别与免疫调控研究领域近年来国际上的前沿工作进行了总结与分析，通过自行绘制的一张示意图，归纳了该领域的研究进展，同时提出了此研究领域目前尚未解决、有待于进一步探索和深入研究的六方面研究内容和未来方向。

 

此外，近期曹雪涛院士还在《Blood》杂志上发表文章Fibronectin maintains survival of mouse NK cells via CD11b/Src/{beta}-catenin pathway，解析自然杀伤细胞的免疫功能。

 

两原文检索

 News and Views

Nature Immunology 10, 1049 - 1051 (2009)

doi:10.1038/ni1009-1049

New DNA-sensing pathway feeds RIG-I with RNA

Xuetao Cao1

Xuetao Cao is in the National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.

e-mail: [e-mail]

【Abstract】

Cytosolic DNA sensors have remained poorly defined so far. Two recent studies identify a previously undefined cytosolic DNA-sensing pathway that depends on the RNA polymerase III–mediated conversion of microbial DNA into 5'-triphosphate double-stranded RNA that activates the RNA helicase RIG-I.

 

Blood. 2009 Sep 8. [Epub ahead of print]

Fibronectin maintains survival of mouse NK cells via CD11b/Src/{beta}-catenin pathway.

Zhang T, Liu S, Yang P, Han C, Wang J, Liu J, Han Y, Yu Y, Cao X.

Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.

 

Tissue microenvironment and stroma-derived extracellular matrix (ECM) molecules play important roles in the survival and differentiation of cells. Mouse natural killer (NK) cells usually die within 24 hours once isolated ex vivo. Exogenous cytokines such as interleukin (IL)-12 and IL-15 are required to maintain the survival and activity of mouse NK cells cultured in vitro. However, whether and how ECM molecules such as fibronectin can support the survival of NK cells remain unknown. Here we demonstrate that fibronectin, just like IL-15, can maintain survival of mouse NK cells in vitro. Furthermore, we show that fibronectin binds to the CD11b on NK cells, and then CD11b recruits and activates Src. Src can directly interact with beta-catenin and trigger nuclear translocation of beta-catenin. The activation of beta-catenin promotes ERK phosphorylation, resulting in the increased expression of anti-apoptotic protein Bcl-2 which may contribute to the maintenance of NK cell survival. Consistently, fibronectin can not maintain the survival of CD11b negative NK cells and beta-catenin-deficient NK cells sorted from in vivo, and the number of NK cell is dramatically decreased in the beta-catenin-deficient mice. Therefore, fibronectin can maintain survival of mouse NK cells by activating ERK and upregulating Bcl-2 expression via CD11b/Src/beta-catenin pathway.

PMID: 19738028 [PubMed - as supplied by publisher]