在青春期同伴受害改变基因表达和细胞因子谱在过渡到成年

IF 3.5 Q2 IMMUNOLOGY
Jens Heumann , Steve W. Cole , Manuel Eisner , Denis Ribeaud , Edna Grünblatt , Michael J. Shanahan
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引用次数: 0

摘要

经历同伴伤害(PV)的青少年经常报告心身疾病;然而,人们对潜在的分子效应知之甚少。社会逆境已经被证明可以下调免疫基因,上调炎症基因。本研究从基因表达、白细胞组成和细胞因子水平等方面研究了PV潜在的持久分子效应。参与者(n = 144;47%女性)来自苏黎世脑和免疫基因研究(z-GIG)。在11岁至20岁期间研究PV,在22岁时收集分子数据。一个反事实框架与遗传信息逆概率加权被应用于解释个人和环境混杂因素。与非pv对照相比,受害者表现出广泛的免疫变化。计算机反褶积显示白细胞组成的变化,包括m2样单核细胞偏斜。差异表达基因富集于几个Reactome通路,包括干扰素信号、代谢、信号转导、染色质组织和蛋白质代谢。转录因子STAT2和IRF2是关键的调节因子,其靶基因主要在干扰素信号通路和染色质组织通路中。细胞因子水平也有所不同,包括促炎标志物如CCL4、TNF、CXCL9和CXCL10升高。这些发现为PV的免疫调节潜力提供了初步证据,并强调了旨在预防、建立复原力和减轻长期影响的公共卫生战略的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Peer victimization in adolescence alters gene expression and cytokine profiles during transition to adulthood
Adolescents who experience peer victimization (PV) often report psychosomatic complaints; however, little is known about possible underlying molecular effects. Social adversity has already been shown to downregulate immune genes and upregulate inflammatory genes. This study investigated PV for potentially enduring molecular effects, in terms of gene expression, leukocyte composition, and cytokine levels in young adulthood. Participants (n = 144; 47% female) were drawn from the Zurich Brain and Immune Gene Study (z-GIG). PV was studied from age 11 to 20, and molecular data were collected at age 22. A counterfactual framework with genetically informed inverse probability weighting was applied to account for individual and environmental confounders. Compared to non-PV controls, victims showed extensive immune changes. In silico deconvolution revealed shifts in leukocyte composition, including an M2-like monocyte–skewed profile. Differentially expressed genes were enriched in several Reactome pathways, including Interferon signaling, Metabolism, Signal transduction, Chromatin Organization, and Metabolism of Proteins. Transcription factors STAT2 and IRF2 emerged as key regulators, with target genes primarily in the Interferon Signaling and Chromatin Organization pathways. Cytokine levels also differed, including elevated pro-inflammatory markers such as CCL4, TNF, CXCL9, and CXCL10. The findings provide preliminary evidence of the immunomodulatory potential of PV and highlight the importance of public health strategies aimed at prevention, building resilience, and mitigating long-term effects.
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来源期刊
Brain, behavior, & immunity - health
Brain, behavior, & immunity - health Biological Psychiatry, Behavioral Neuroscience
CiteScore
8.50
自引率
0.00%
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0
审稿时长
97 days
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