Altered transcriptional and chromatin responses to rhinovirus in bronchial epithelial cells from adults with asthma.
Altered transcriptional and chromatin responses to rhinovirus in bronchial epithelial cells from adults with asthma.
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DOI：
10.1038/s42003-020-01411-4
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发表时间：
2020-11-13
影响因子：
5.9
通讯作者：
Ober C
中科院分区：
文献类型：
--
作者：
Helling BA;Sobreira DR;Hansen GT;Sakabe NJ;Luo K;Billstrand C;Laxman B;Nicolae RI;Nicolae DL;Bochkov YA;Gern JE;Nobrega MA;White SR;Ober C
鼻病毒（RV）感染与哮喘的发生和临床表现之间存在终身关系。在这项研究中，我们证明，培养的原代支气管上皮细胞从成人哮喘（n = 9）显示不同的转录和染色质反应RV感染相比，那些没有哮喘（n = 9）。与对照组相比，哮喘病例的细胞中对RV的转录和染色质反应的数量和幅度都被抑制。转录响应基因的通路分析显示，对照组中细胞凋亡通路丰富，而哮喘病例中炎症通路丰富。使用启动子捕获Hi-C，我们将RV反应性染色质区域与RV反应性基因连接，并显示这些区域和基因在哮喘GWAS位点富集。总之，我们的研究表明，哮喘病例的细胞中存在延迟或延长的炎症状态，并突出了可能导致哮喘遗传风险的基因。Britney Helling等报道，与来自无哮喘个体的细胞相比，来自哮喘成人的培养支气管细胞在暴露于鼻病毒时显示出不同的基因表达和染色质可及性模式。他们的数据表明，与没有哮喘的人相比，鼻病毒感染导致哮喘患者的炎症基因激活延迟或延长。
There is a life-long relationship between rhinovirus (RV) infection and the development and clinical manifestations of asthma. In this study we demonstrate that cultured primary bronchial epithelial cells from adults with asthma (n = 9) show different transcriptional and chromatin responses to RV infection compared to those without asthma (n = 9). Both the number and magnitude of transcriptional and chromatin responses to RV were muted in cells from asthma cases compared to controls. Pathway analysis of the transcriptionally responsive genes revealed enrichments of apoptotic pathways in controls but inflammatory pathways in asthma cases. Using promoter capture Hi-C we tethered regions of RV-responsive chromatin to RV-responsive genes and showed enrichment of these regions and genes at asthma GWAS loci. Taken together, our studies indicate a delayed or prolonged inflammatory state in cells from asthma cases and highlight genes that may contribute to genetic risk for asthma. Britney Helling et al. report that cultured bronchial cells from adults with asthma show different gene expression and chromatin accessibility patterns when exposed to rhinovirus than do cells from individuals without asthma. Their data suggest that rhinovirus infection leads to a delayed or elongated activation of inflammatory genes in individuals with asthma compared to those without asthma.