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孕期内空气污染暴露对细胞因子和组蛋白修饰谱的单细胞水平影响。

Impact of air pollution exposure on cytokines and histone modification profiles at single-cell levels during pregnancy.

机构信息

Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.

School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.

出版信息

Sci Adv. 2024 Nov 29;10(48):eadp5227. doi: 10.1126/sciadv.adp5227.

DOI:10.1126/sciadv.adp5227
PMID:39612334
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11606498/
Abstract

Fine particulate matter (PM) exposure can induce immune system pathology via epigenetic modification, affecting pregnancy outcomes. Our study investigated the association between PM exposure and immune response, as well as epigenetic changes using high-dimensional epigenetic landscape profiling using cytometry by time-of-flight (EpiTOF) at the single cell. We found statistically significant associations between PM exposure and levels of certain cytokines [interleukin-1RA (IL-1RA), IL-8/CXCL8, IL-18, and IL-27)] and histone posttranslational modifications (HPTMs) in immune cells (HPTMs: H3K9ac, H3K23ac, H3K27ac, H2BK120ub, H4K20me1/3, and H3K9me1/2) among pregnant and nonpregnant women. The cord blood of neonates with high maternal PM exposure showed lower IL-27 than those with low exposure. Furthermore, PM exposure affects the co-modification profiles of cytokines between pregnant women and their neonates, along with HPTMs in each immune cell type between pregnant and nonpregnant women. These modifications in specific histones and cytokines could indicate the toxicological mechanism of PM exposure in inflammation, inflammasome pathway, and pregnancy complications.

摘要

细颗粒物（PM）暴露可通过表观遗传修饰诱导免疫系统病理，从而影响妊娠结局。本研究使用流式细胞术时间飞行（EpiTOF）的高维表观遗传景观分析，在单细胞水平上研究了 PM 暴露与免疫反应以及表观遗传变化之间的关系。我们发现，PM 暴露与某些细胞因子（白细胞介素-1 受体拮抗剂（IL-1RA）、白细胞介素-8/CXCL8、白细胞介素-18 和白细胞介素-27）水平以及免疫细胞中的组蛋白翻译后修饰（HPTMs）[H3K9ac、H3K23ac、H3K27ac、H2BK120ub、H4K20me1/3 和 H3K9me1/2]之间存在统计学显著关联，这些关联在孕妇和非孕妇中均存在。高母体 PM 暴露的新生儿脐带血中的 IL-27 低于低暴露组。此外，PM 暴露会影响孕妇及其新生儿之间细胞因子的共同修饰谱，以及孕妇和非孕妇之间每个免疫细胞类型中的 HPTM。这些特定组蛋白和细胞因子的修饰可能表明 PM 暴露在炎症、炎症小体途径和妊娠并发症中的毒理学机制。

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Oxidative stress contributes to hypermethylation of Histone H3 lysine 9 in placental trophoblasts from preeclamptic pregnancies.氧化应激导致子痫前期胎盘滋养细胞组蛋白 H3 赖氨酸 9 的过度甲基化。
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