Immunosenescence-Related Transcriptomic and Immunologic Changes in Older Individuals Following Influenza Vaccination.
Immunosenescence-Related Transcriptomic and Immunologic Changes in Older Individuals Following Influenza Vaccination.
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DOI：
10.3389/fimmu.2016.00450
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发表时间：
2016
影响因子：
7.3
通讯作者：
Poland GA
中科院分区：
文献类型：
--
作者：
Kennedy RB;Ovsyannikova IG;Haralambieva IH;Oberg AL;Zimmermann MT;Grill DE;Poland GA
每年接种流感疫苗的目标是通过产生保护性免疫反应来减少与这种疾病相关的死亡率和发病率。本研究的目的是检查免疫衰老的标志物，并在接受季节性流感A/H1N1疫苗接种的老年研究人群中，确定与免疫衰老相关的基因表达、基因调控、细胞因子分泌和免疫学变化。令人惊讶的是，这一队列中先前的研究显示，免疫衰老标志物与接种疫苗的体液免疫反应之间的相关性很弱。在这份报告中，我们进一步研究了每个免疫衰老标志物(年龄、T细胞受体切除环频率、端粒酶表达、CD2 8CD4+T细胞百分率、CD2 8CD8+T细胞百分率、CD8CD8T细胞比率)与其他免疫反应标志物(血清细胞因子和趋化因子表达)以及基因表达和/或调节的关系。许多免疫衰老标记确实与不同的个体DNA甲基化位点、miRNA表达水平、mRNA表达水平、血清细胞因子和白细胞亚群相关。然而，当单个免疫衰老标志物按途径或功能术语分组时，发现了几个共同的生物学功能：抗原处理和提呈途径、MAPK、mTOR、TCR、BCR和钙信号通路，以及关键的细胞代谢、增殖和生存活动。此外，缺乏CD28表达的CD4+和/或CD8+T细胞的百分比也与调节已知与病毒感染有关的基因簇的miRNAs相关。对免疫衰老相关途径和基因集的综合(DNA甲基化、mRNA、miRNA和蛋白质水平)网络生物学分析确定了两条已知的途径(例如，趋化因子信号、CTL和NK细胞活性)，以及一个先前未用已知功能注释的基因表达模块。这些结果可能会提高我们预测流感免疫反应的能力，并有助于新疫苗的开发，并突出了更多研究的必要性，以更好地定义和表征免疫衰老。
The goal of annual influenza vaccination is to reduce mortality and morbidity associated with this disease through the generation of protective immune responses. The objective of the current study was to examine markers of immunosenescence and identify immunosenescence-related differences in gene expression, gene regulation, cytokine secretion, and immunologic changes in an older study population receiving seasonal influenza A/H1N1 vaccination. Surprisingly, prior studies in this cohort revealed weak correlations between immunosenescence markers and humoral immune response to vaccination. In this report, we further examined the relationship of each immunosenescence marker (age, T cell receptor excision circle frequency, telomerase expression, percentage of CD28− CD4+ T cells, percentage of CD28− CD8+ T cells, and the CD4/CD8 T cell ratio) with additional markers of immune response (serum cytokine and chemokine expression) and measures of gene expression and/or regulation. Many of the immunosenescence markers indeed correlated with distinct sets of individual DNA methylation sites, miRNA expression levels, mRNA expression levels, serum cytokines, and leukocyte subsets. However, when the individual immunosenescence markers were grouped by pathways or functional terms, several shared biological functions were identified: antigen processing and presentation pathways, MAPK, mTOR, TCR, BCR, and calcium signaling pathways, as well as key cellular metabolic, proliferation and survival activities. Furthermore, the percent of CD4+ and/or CD8+ T cells lacking CD28 expression also correlated with miRNAs regulating clusters of genes known to be involved in viral infection. Integrated (DNA methylation, mRNA, miRNA, and protein levels) network biology analysis of immunosenescence-related pathways and genesets identified both known pathways (e.g., chemokine signaling, CTL, and NK cell activity), as well as a gene expression module not previously annotated with a known function. These results may improve our ability to predict immune responses to influenza and aid in new vaccine development, and highlight the need for additional studies to better define and characterize immunosenescence.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
5.5
作者：
Beyer, Walter E. P.;McElhaney, Janet;Osterhaus, Albert D. M. E.
通讯作者：
Osterhaus, Albert D. M. E.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
4.4
作者：
Hadrup, SR;Strindhall, J;Wikby, A
通讯作者：
Wikby, A