请登录|免费注册|
ENGLISH 简体中文
您当前的位置:首页 > 技术资源 > 客户文章

Long noncoding RNA derived from CD244 signalingepigenetically controls CD8+ T-cell immuneresponses in tuberculosis infection

发布日期:2016/7/28 15:04:40

期刊名称:Proceedings of the National Academy of Sciences

期刊号:DOI: 10.1073/pnas.1501662112.

通迅作者:Yang Wang, HuilingZhong, XiaodanXie

作者单位:中山大学

使用产品与服务:siRNA

文章摘要:

Molecular mechanisms for T-cell immune responses modulated by T cell-inhibitory molecules during tuberculosis (TB) infection remain unclear. Here, we show that active human TB infection up-regulates CD244 and CD244 signaling-associated molecules in CD8(+) T cells and that blockade of CD244 signaling enhances production of IFN-γ and TNF-α. CD244 expression/signaling in TB correlates with high levels of a longnoncoding RNA (lncRNA)-BC050410 [named as lncRNA-AS-GSTT1(1-72) or lncRNA-CD244] in the CD244(+)CD8(+) T-cell subpopulation. CD244signaling drives lncRNA-CD244 expression via sustaining a permissive chromatin state in the lncRNA-CD244 locus. By recruiting polycomb protein enhancer of zeste homolog 2 (EZH2) to infg/tnfa promoters, lncRNA-CD244 mediates H3K27 trimethylation at infg/tnfa loci toward repressive chromatin states and inhibits IFN-γ/TNF-α expression in CD8(+) T cells. Such inhibition can be reversed by knock down of lncRNA-CD244. Interestingly, adoptive transfer of lncRNA-CD244-depressed CD8(+) T cells to Mycobacterium tuberculosis (MTB)-infected mice reduced MTB infection and TB pathology compared with lncRNA-CD244-expressed controls. Thus, this work uncovers previously unidentified mechanisms in which T cell-inhibitory signaling and lncRNAs regulate T-cell responses and host defense against TB infection.

实验结果:




原文链接:点击打开




版权所有:广州市锐博生物科技有限公司 Copyright©2013 Guangzhou RiboBio Co., Ltd.
地址:广州开发区科学城科学大道182号创新大厦C3区13-14层   邮编:510663   粤ICP备05022931号   浏览器建议:IE8.0 1024X768分辨率
主营产品及服务:piRNA  寡核酸  siRNA  miRNA  microRNA   RNAi  shRNA  lncRNA  ncRNA  细胞增殖  生物芯片  高通量测序