最新一期的《自然：免疫學(xué)》(Nature Immunology)雜志報(bào)道了浙大醫(yī)學(xué)院求是特聘教授項(xiàng)春生博士與中國(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)研究所孫兵教授領(lǐng)導(dǎo)的研究小組的最新合作研究成果。研究人員通過小鼠模型發(fā)現(xiàn)，在先天性免疫系統(tǒng)中有一個(gè)非常關(guān)鍵的調(diào)控分子,，它能有效調(diào)控機(jī)體內(nèi)的免疫應(yīng)答信號(hào)通路,，形成既有效、又不過度的免疫平衡狀態(tài),。
研究人員用自行研制的小鼠全基因組DNA芯片技術(shù)在LPS誘導(dǎo)的DC細(xì)胞分化過程中篩選出一個(gè)重要的基因，新的免疫負(fù)性調(diào)控因子Trim30α，并發(fā)現(xiàn)這種分子在炎癥的初始階段被誘導(dǎo)產(chǎn)生,，與TAB2/3結(jié)合并導(dǎo)致其降解；TAB2/3的降解引起Traf6的自身泛素化,，最終阻斷NF-kB的信號(hào)通路,，從而在DC細(xì)胞，對(duì)致炎因子如IL-6和TNF-α的產(chǎn)生起到明顯的抑制作用,。正常的免疫應(yīng)答對(duì)機(jī)體抵抗感染是非常必要的,，而過度的免疫應(yīng)答又會(huì)對(duì)機(jī)體產(chǎn)生損害，該研究揭示了炎癥抑制方面一個(gè)新的免疫機(jī)制,。這一發(fā)現(xiàn)對(duì)人們深入了解免疫系統(tǒng)的調(diào)控網(wǎng)絡(luò)具有重要意義,。
項(xiàng)春生博士于2006年被浙江加州國(guó)際納米技術(shù)研究院聘為分子診斷平臺(tái)的首席科學(xué)家。目前是醫(yī)學(xué)院附屬第一醫(yī)院傳染病診治國(guó)家重點(diǎn)實(shí)驗(yàn)室的求是特聘教授,。作為該課題的主要參與者,，項(xiàng)春生博士用DNA芯片技術(shù)在篩選特定基因的研究中，做出了重要的貢獻(xiàn),。
生物谷推薦原始出處：
Nature Immunology 9, 369 - 377 (2008) Published online: 16 March 2008 | doi:10.1038/ni1577
TRIM30 negatively regulates TLR-mediated NF-B activation by targeting TAB2 and TAB3 for degradation
Mude Shi1,6, Weiwen Deng1,6, Enguang Bi1, Kairui Mao1, Yongyong Ji1, Guomei Lin1, Xiaodong Wu1, Zhiyun Tao1, Zhenhu Li1, Xinfen Cai1, Shuhui Sun2, Charlie Xiang3 & Bing Sun1,4,5
Abstract
Toll-like receptor (TLR) signaling is pivotal to innate and adaptive immune responses and must be tightly controlled. The mechanisms of TLR signaling have been the focus of extensive studies. Here we report that the tripartite-motif protein TRIM30, a RING protein, was induced by TLR agonists and interacted with the TAB2-TAB3-TAK1 adaptor-kinase complex involved in the activation of transcription factor NF-B. TRIM30 promoted the degradation of TAB2 and TAB3 and inhibited NF-B activation induced by TLR signaling. In vivo studies showed that transfected or transgenic mice overexpressing TRIM30 were more resistant to endotoxic shock. Consistent with that, in vivo 'knockdown' of TRIM30 mRNA by small interfering RNA impaired lipopolysaccharide-induced tolerance. Finally, expression of TRIM30 depended on NF-B activation. Our results collectively indicate that TRIM30 negatively regulates TLR-mediated NF-B activation by targeting degradation of TAB2 and TAB3 by a 'feedback' mechanism.
