Differential Effects of Environmental and Genetic Factors on T and B Cell Immune Traits.
Differential Effects of Environmental and Genetic Factors on T and B Cell Immune Traits.
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DOI：
10.1016/j.celrep.2016.10.053
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发表时间：
2016-11-22
期刊：
影响因子：
8.8
通讯作者：
Koenen HJPM
中科院分区：
文献类型：
--
作者：
Aguirre-Gamboa R;Joosten I;Urbano PCM;van der Molen RG;van Rijssen E;van Cranenbroek B;Oosting M;Smeekens S;Jaeger M;Zorro M;Withoff S;van Herwaarden AE;Sweep FCGJ;Netea RT;Swertz MA;Franke L;Xavier RJ;Joosten LAB;Netea MG;Wijmenga C;Kumar V;Li Y;Koenen HJPM
有效的免疫需要一个复杂的细胞和体液成分网络，这些成分相互作用，并受不同的环境和宿主因素的影响。我们使用系统生物学方法，从人类功能基因组学项目的1500名健康志愿者中全面评估了环境和遗传因素对外周血免疫细胞群体的影响，包括与免疫球蛋白浓度的相关性。遗传遗传力估计表明，T细胞数量的变化更强烈地受到遗传因素的影响，而B细胞计数更受环境影响。数量性状位点（QTL）定位确定了8个独立的基因组位点与白细胞计数的变化，包括四个协会与T和B细胞亚型。在全基因组关联研究（GWAS）SNP中富集了所鉴定的QTL，这些SNP被报道为增加对免疫介导的疾病的易感性。我们的系统方法提供了对人类细胞和体液免疫性状变异性的见解。了解免疫细胞和免疫球蛋白水平的个体间差异季节和性别影响B细胞亚群丰度可能调节血液中B细胞水平的遗传位点的鉴定细胞计数QTL与（自身）免疫/炎症疾病的风险SNP重叠作为人类功能基因组学项目的一部分，这项由Aguirre-Gamboa等人进行的研究。绘制遗传和非遗传因素对免疫细胞计数和免疫球蛋白水平的影响。他们发现季节和性别影响大多数B细胞亚群的丰度。
Effective immunity requires a complex network of cellular and humoral components that interact with each other and are influenced by different environmental and host factors. We used a systems biology approach to comprehensively assess the impact of environmental and genetic factors on immune cell populations in peripheral blood, including associations with immunoglobulin concentrations, from ∼500 healthy volunteers from the Human Functional Genomics Project. Genetic heritability estimation showed that variations in T cell numbers are more strongly driven by genetic factors, while B cell counts are more environmentally influenced. Quantitative trait loci (QTL) mapping identified eight independent genomic loci associated with leukocyte count variation, including four associations with T and B cell subtypes. The QTLs identified were enriched among genome-wide association study (GWAS) SNPs reported to increase susceptibility to immune-mediated diseases. Our systems approach provides insights into cellular and humoral immune trait variability in humans. Understanding inter-individual variation of immune cells and immunoglobulin levels Season and gender influence B cell subpopulation abundance Identification of genetic loci that might regulate B cell levels in blood Cell count QTLs overlap with risk SNPs for (auto)immune/inflammatory disease As part of the Human Functional Genomics Project, this study by Aguirre-Gamboa et al. maps the contribution of genetics and non-heritable factors onto immune-cell counts and immunoglobulin levels. They find that season and gender influence the abundance of most of B cell subpopulations.
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通讯作者：
Liston A