Wang X, Wang J, Xing C-Y, Zang R, Pu Y-Y, Yin Z-X
Department of Respiration Мedicine, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong Province, 250013 China.
Department of Community Health, Jinan Blood Supply Center, Jinan, Shandong Province, 250001, China.
Mol Biol (Mosk). 2015 May-Jun;49(3):482-90. doi: 10.7868/S0026898415030180.
The role of CD8^(+) T cells in asthma has not been fully discussed. The mechanisms of CD4^(+) and CD8^(+) cells in severe asthma (SA) development were compared. The microarray data (GSE31773) was downloaded from the Gene Expression Omnibus (GEO) database, including 20 samples of CD4^(+) and CD8^(+) T cells, which were collected from 8 health controls (HC), 4 non-severe asthma (NSA) and 8 SA patients. DEGs of CD4^(+) and CD8^(+) T cells in the HC vs. NSA and HC vs. SA groups were identified using the limma package in R. GO and pathway enrichment analysis of the common DEGs between the two groups were analyzed using DAVID. The interactive network of DEGs and significant modules were further explored. In CD4^(+) cells, there were 168 DEGs in HC vs. NSA group and 685 DEGs in HC vs. SA group, while for CD8^(+) T cells there were 719 DEGs in the HC vs. NSA groups and 1255 DEGs in the HC vs. SA groups. Besides, 80 common DEGs from CD4^(+) samples were enriched in the MAPKKK cascade and molecular metabolism, and 385 common DEGs of CD8^(+) T cells were significantly related with cell apoptosis and transformation. Moreover, two significant modules of DEGs in CD4^(+) were found to be involved with MPO and BPI. One module of CD8^(+) T cells containing PDHA1 and MRPL42 was identified to be related with glycolysis. In conclusion, MPO and BPI in CD4^(+), and PDHA1 and MRPL42 in CD8^(+) T cells might be used as specific biomarkers of SA progression. Therapy targeting the functions of CD4^(+) and CD8^(+) T cells may provide a novel perspective for SA treatment.
CD8⁺ T细胞在哮喘中的作用尚未得到充分探讨。比较了CD4⁺和CD8⁺细胞在重度哮喘（SA）发生发展中的机制。从基因表达综合数据库（GEO）下载微阵列数据（GSE31773），其中包括从8名健康对照（HC）、4名非重度哮喘（NSA）患者和8名SA患者收集的20个CD4⁺和CD8⁺ T细胞样本。使用R语言中的limma软件包鉴定HC与NSA组以及HC与SA组中CD4⁺和CD8⁺ T细胞的差异表达基因（DEG）。使用DAVID对两组之间的共同DEG进行基因本体（GO）和通路富集分析。进一步探索DEG的交互网络和重要模块。在CD4⁺细胞中，HC与NSA组有168个DEG，HC与SA组有685个DEG；而对于CD8⁺ T细胞，HC与NSA组有719个DEG，HC与SA组有1255个DEG。此外，来自CD4⁺样本的80个共同DEG在MAPKKK级联反应和分子代谢中富集，CD8⁺ T细胞的385个共同DEG与细胞凋亡和转化显著相关。此外，发现CD4⁺中两个重要的DEG模块与髓过氧化物酶（MPO）和杀菌/通透性增加蛋白（BPI）有关。鉴定出一个包含丙酮酸脱氢酶E1α亚基（PDHA1）和线粒体核糖体蛋白L42（MRPL42）的CD8⁺ T细胞模块与糖酵解有关。总之，CD4⁺中的MPO和BPI以及CD8⁺ T细胞中的PDHA1和MRPL42可能用作SA进展的特异性生物标志物。针对CD4⁺和CD8⁺ T细胞功能的治疗可能为SA治疗提供新的视角。
