期刊
CELL
卷 167, 期 4, 页码 1111-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2016.10.018
关键词
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资金
- ERC Consolidator Grant [310372]
- Spinoza grant [94-212]
- IN-CONTROL CVON grant [CVON2012-03]
- ERC Advanced Grant (ERC) [2012-322698]
- Spinoza Prize [NWO SPI 92-266]
- Dutch Digestive Diseases Foundation [MLDS WO11-30]
- European Union's Seventh Framework Programme (EU FP7) TANDEM project [HEALTH-F3-2012-305279]
- Netherlands Organization for Scientific Research (NWO) VENI grant [863.13.011]
- Interleukin Foundation
- NIH grant [AI15614]
- STW grant [STW13546]
- BBMRI-NL
- Netherlands Organization for Scientific Research (NWO) [184.021.007]
Differences in susceptibility to immune-mediated diseases are determined by variability in immune responses. In three studies within the Human Functional Genomics Project, we assessed the effect of environmental and non-genetic host factors of the genetic make-up of the host and of the intestinal microbiome on the cytokine responses in humans. We analyzed the association of these factors with circulating mediators and with six cytokines after stimulation with 19 bacterial, fungal, viral, and non-microbial metabolic stimuli in 534 healthy subjects. In this first study, we show a strong impact of non-genetic host factors (e.g., age and gender) on cytokine production and circulating mediators. Additionally, annual seasonality is found to be an important environmental factor influencing cytokine production. Alpha-1-antitrypsin concentrations partially mediate the seasonality of cytokine responses, whereas the effect of vitamin D levels is limited. The complete dataset has been made publicly available as a comprehensive resource for future studies.
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