Yi Zhengjun, Li Jianhua, Gao Kunshan, Fu Yurong
Department of Laboratory Medicine of Affiliated Hospital of Weifang Medical University, Key Laboratory of Clinical Laboratory Diagnostics in Universities of Shandong, Weifang Medical University, Weifang 261031, China.
Department of Medical Microbiology, Weifang Medical University, Weifang 261053, China.
J Infect. 2014 Dec;69(6):558-68. doi: 10.1016/j.jinf.2014.06.016. Epub 2014 Jun 27.
To identify differentially expressed long non-coding RNAs (lncRNAs) in CD4(+) T cells triggered upon latent tuberculosis (TB) infection.
Expression profiles of lncRNAs and mRNAs in CD4(+) T cells from individuals with latent TB infection (LTBI), active TB and healthy controls were analyzed by microarray assay and four lncRNAs were selected for validation using real time-quantitative polymerase chain reaction (RT-qPCR). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway based approaches were used to investigate biological functions and signaling pathways affected by the differentially expressed mRNAs.
LncRNAs and mRNAs in CD4(+) T cells were involved in LTBI and active TB disease. Compared with healthy controls, 449 lncRNAs and 461 mRNAs were deregulated in LTBI group, 1,113 lncRNAs and 1,490 mRNAs were deregulated in active TB group, as well as 163 lncRNAs and 187 mRNAs were differentially expressed in both LTBI and active TB group. It was worth noting that 41 lncRNAs and 60 mRNAs were deregulated between three groups. Most deregulated lncRNAs were from intergenic regions (∼ 50%), natural antisense to protein-coding loci (∼ 20%), or intronic antisense to protein-coding loci (∼ 10%). Significantly enriched signaling pathways based on deregulated mRNAs were mainly involved in mitogen-activated protein kinase (MAPK) signaling pathway, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, etc.
The study was the first report of differentially expressed lncRNAs in CD4(+) T cells response to TB infection and indicated that some lncRNAs may be involved in regulating host immune response to TB infection. Future studies are needed to further elucidate potential roles of these deregulated lncRNAs in LTBI and its reactivation.
鉴定潜伏性结核感染时触发的CD4(+) T细胞中差异表达的长链非编码RNA（lncRNA）。
通过微阵列分析检测潜伏性结核感染（LTBI）患者、活动性结核患者及健康对照者CD4(+) T细胞中lncRNA和mRNA的表达谱，并选择4种lncRNA使用实时定量聚合酶链反应（RT-qPCR）进行验证。采用基于基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路的方法研究差异表达mRNA所影响的生物学功能和信号通路。
CD4(+) T细胞中的lncRNA和mRNA参与了LTBI和活动性结核疾病。与健康对照相比，LTBI组中有449种lncRNA和461种mRNA表达失调，活动性结核组中有1113种lncRNA和1490种mRNA表达失调，且在LTBI组和活动性结核组中均有163种lncRNA和187种mRNA差异表达。值得注意的是，三组之间有41种lncRNA和60种mRNA表达失调。大多数表达失调的lncRNA来自基因间区域（约50%）、蛋白质编码基因座的天然反义链（约20%）或蛋白质编码基因座的内含子反义链（约10%）。基于表达失调mRNA的显著富集信号通路主要涉及丝裂原活化蛋白激酶（MAPK）信号通路、细胞因子-细胞因子受体相互作用、Toll样受体信号通路等。
该研究首次报道了CD4(+) T细胞对结核感染反应中差异表达的lncRNA，并表明一些lncRNA可能参与调节宿主对结核感染的免疫反应。未来需要进一步研究以阐明这些表达失调的lncRNA在LTBI及其激活中的潜在作用。
