Time-Resolved Gene Expression Analysis Monitors the Regulation of Inflammatory Mediators and Attenuation of Adaptive Immune Response by Vitamin D.
Time-Resolved Gene Expression Analysis Monitors the Regulation of Inflammatory Mediators and Attenuation of Adaptive Immune Response by Vitamin D.
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DOI：
10.3390/ijms23020911
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发表时间：
2022-01-14
影响因子：
5.6
通讯作者：
Carlberg C
中科院分区：
文献类型：
--
作者：
Hanel A;Carlberg C
外周血单个核细胞（PBMC）属于先天性和适应性免疫系统，对全身环境的变化高度敏感和响应。在这项研究中，我们重点研究了活性维生素D代谢物1α，25-二羟基维生素D3（1，25（OH）2D 3）刺激后4、8、24和48 h新鲜分离的人PBMC中转录变化的时间过程。将所有四个时间点放在一起，鉴定了662个靶基因，并通过差异基因表达的时间将其分离为179个主要靶和483个次要靶，或通过表达变化的驱动因素将其分离为293个直接靶和369个间接靶。后一种分类显示，超过50%的靶基因主要由细胞对离体暴露的反应驱动，而不是由核激素驱动，这在很大程度上解释了其下调效应。功能分析表明维生素D通过下调10个主要组织相容性复合物II类基因、S100钙结合蛋白A家族的5个alarmins和通过影响C-X-C基序配体家族的6个趋化因子在抑制炎症和适应性免疫应答中的作用。总之，研究时间分辨反应可以更好地了解维生素D对免疫系统的影响。
Peripheral blood mononuclear cells (PBMCs) belong to the innate and adaptive immune system and are highly sensitive and responsive to changes in their systemic environment. In this study, we focused on the time course of transcriptional changes in freshly isolated human PBMCs 4, 8, 24 and 48 h after onset of stimulation with the active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). Taking all four time points together, 662 target genes were identified and segregated either by time of differential gene expression into 179 primary and 483 secondary targets or by driver of expression change into 293 direct and 369 indirect targets. The latter classification revealed that more than 50% of target genes were primarily driven by the cells' response to ex vivo exposure than by the nuclear hormone and largely explained its down-regulatory effect. Functional analysis indicated vitamin D’s role in the suppression of the inflammatory and adaptive immune response by down-regulating ten major histocompatibility complex class II genes, five alarmins of the S100 calcium binding protein A family and by affecting six chemokines of the C-X-C motif ligand family. Taken together, studying time-resolved responses allows to better contextualize the effects of vitamin D on the immune system.
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影响因子：
4.1
作者：
Carlberg, Carsten
通讯作者：
Carlberg, Carsten
影响因子：
14.9
作者：
Heikkinen S;Väisänen S;Pehkonen P;Seuter S;Benes V;Carlberg C
通讯作者：
Carlberg C
影响因子：
5
作者：
Handunnetthi, L.;Ramagopalan, S. V.;Ebers, G. C.;Knight, J. C.
通讯作者：
Knight, J. C.
影响因子：
4
作者：
Bendik I;Friedel A;Roos FF;Weber P;Eggersdorfer M
通讯作者：
Eggersdorfer M
影响因子：
6.1
作者：
Haussler, Mark R.;Haussler, Carol A.;Jurutka, Peter W.
通讯作者：
Jurutka, Peter W.