1月9日 Nature Immunology 雜志網(wǎng)絡(luò)版刊登了中科院上海生科院生化與細(xì)胞所孫兵研究組的最新研究成果,。Th2細(xì)胞是一種重要的輔助性T細(xì)胞亞群，其在抗寄生蟲感染,，誘導(dǎo)系統(tǒng)性紅斑狼瘡,，過(guò)敏性疾病及哮喘等疾病中發(fā)揮關(guān)鍵性作用,。孫兵研究組從Th2細(xì)胞中尋找到一種新的功能性細(xì)胞外基質(zhì)蛋白（Extracellular Matrix protein 1:ECM1）,，ECM1可以調(diào)控Th2細(xì)胞表面趨化因子受體S1P1的表達(dá),，進(jìn)而選擇性地控制Th2細(xì)胞從淋巴結(jié)中向外周炎癥灶遷移。這一發(fā)現(xiàn)為我們深入了解Th2細(xì)胞的遷移調(diào)控和過(guò)敏性疾病的發(fā)生進(jìn)程有重要的科學(xué)意義。
幼稚T細(xì)胞在淋巴結(jié)中被抗原遞呈細(xì)胞活化,，分化成熟為不同的效應(yīng)性T細(xì)胞,。這些細(xì)胞將遷移至病灶部位發(fā)揮功能。T細(xì)胞的遷移在時(shí)間和空間上被精確調(diào)節(jié),。在這調(diào)節(jié)過(guò)程中,，趨化因子受體S1P1在T細(xì)胞的表達(dá)調(diào)控，對(duì)細(xì)胞的遷移發(fā)揮著重要作用,，但其調(diào)控機(jī)制有待澄清,。
通過(guò)研究Th2細(xì)胞介導(dǎo)的小鼠過(guò)敏性哮喘模型，孫兵研究組的李振虎和張淵博士發(fā)現(xiàn)ECM1在Th2細(xì)胞中被高表達(dá),。利用ECM1基因敲除技術(shù)在過(guò)敏性哮喘小鼠模型中證明ECM1的缺失會(huì)導(dǎo)致哮喘疾病癥狀的減輕,。ECM1的缺失會(huì)使Th2細(xì)胞停留在淋巴結(jié)中，而在Th1細(xì)胞中不存在這種現(xiàn)象,。研究機(jī)制表明：在Th2細(xì)胞活化的晚期,，其所分泌ECM1分子與Th2細(xì)胞表面的白介素2受體的β亞基相互作用，進(jìn)而抑制IL-2介導(dǎo)的STAT5磷酸化,，從而解除對(duì)轉(zhuǎn)錄調(diào)控因子klf2的抑制作用,，促進(jìn)S1P1的表達(dá)，并最終促進(jìn)T細(xì)胞的遷移,。這些發(fā)現(xiàn)有助于我們更好的理解Th2細(xì)胞的遷移和其所介導(dǎo)的免疫性疾病的關(guān)系,。我們的研究工作提示，ECM1有可能作為過(guò)敏性哮喘治療的藥物靶標(biāo),。
此項(xiàng)研究成果得到國(guó)家科技部,、國(guó)家自然科學(xué)基金委、中國(guó)科學(xué)院和上海市科委的經(jīng)費(fèi)資助,。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature Immunology doi:10.1038/ni.1983
ECM1 controls TH2 cell egress from lymph nodes through re-expression of S1P1
Zhenhu Li,Yuan Zhang,Zhiduo Liu,Xiaodong Wu,Yuhan Zheng,Zhiyun Tao,Kairui Mao,Jie Wang,Guomei Lin,Lin Tian,Yongyong Ji,Meiling Qin,Shuhui Sun,Xueliang Zhu& Bing Sun
Type 2 helper T cells (TH2) are critically involved in allergies and asthma. Here we demonstrate that extracellular matrix protein-1 (ECM1) is highly and selectively expressed in TH2 cells. ECM1 deficiency caused impaired TH2 responses and reduced allergic airway inflammation in vivo. Functional analysis demonstrated that although the TH2 polarization of ECM1-deficient cells was unimpaired, these cells had a defect in migration and were retained in peripheral lymphoid organs. This was associated with reduced expression of KLF2 and S1P1. We also found that ECM1 could directly bind the interleukin-2 (IL-2) receptor to inhibit IL-2 signaling and activate S1P1 expression. Our data identify a previously unknown function of ECM1 in regulating TH2 cell migration through control of KLF2 and S1P1 expression.
