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空气污染暴露与免疫调节基因的甲基化、免疫细胞谱的改变以及儿童血压升高有关。

Air pollution exposure is linked with methylation of immunoregulatory genes, altered immune cell profiles, and increased blood pressure in children.

机构信息

Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford, CA, 94305, USA.

Department of Medicine, Stanford University, Stanford, CA, 94305, USA.

出版信息

Sci Rep. 2021 Feb 18;11(1):4067. doi: 10.1038/s41598-021-83577-3.

DOI:10.1038/s41598-021-83577-3
PMID:33603036
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7893154/
Abstract

Ambient air pollution exposure is associated with cardiovascular dysregulation and immune system alterations, yet no study has investigated both simultaneously in children. Understanding the multifaceted impacts may provide early clues for clinical intervention prior to actual disease presentation. We therefore determined the associations between exposure to multiple air pollutants and both immunological outcomes (methylation and protein expression of immune cell types associated with immune regulation) and cardiovascular outcomes (blood pressure) in a cohort of school-aged children (6-8 years; n = 221) living in a city with known elevated pollution levels. Exposure to fine particular matter (PM), carbon monoxide (CO), and ozone (O) was linked to altered methylation of most CpG sites for genes Foxp3, IL-4, IL-10 and IFN-g, all involved in immune regulation (e.g. higher PM exposure 1 month prior to the study visit was independently associated with methylation of the IL-4 CpG24 site (est = 0.16; P = 0.0095). Also, immune T helper cell types (Th1, Th2 and Th17) were associated with short-term exposure to PM, O and CO (e.g. Th1 cells associated with PM at 30 days: est = - 0.34, P < 0.0001). Both B cells (est = - 0.19) and CD4+ cells (est = 0.16) were associated with 1 day NO2 exposure (P ≤ 0.031), whereas CD4+ and CD8+ cells were associated with chronic exposure to PAH, NOx and/or NO (P ≤ 0.038 for all). Finally, diastolic BP (DBP) was inversely associated with long-term exposures to both CO and PAH, and both systolic and pulse pressure were associated with short-term NO and chronic NOx exposure. Our findings demonstrate links between air pollution exposure and methylation of immunoregulatory genes, immune cell profiles and blood pressure, suggesting that even at a young age, the immune and cardiovascular systems are negatively impacted by exposure to air pollution.

摘要

大气污染暴露与心血管失调和免疫系统改变有关,但尚无研究同时在儿童中对此进行调查。了解这些多方面的影响可能为实际疾病出现前的临床干预提供早期线索。因此,我们在一个已知污染水平较高的城市中,对一个年龄在 6-8 岁的学龄儿童队列(n=221)进行了研究,以确定多种空气污染物暴露与免疫结果(与免疫调节相关的免疫细胞类型的甲基化和蛋白表达)和心血管结果(血压)之间的关联。细颗粒物(PM)、一氧化碳(CO)和臭氧(O)的暴露与大多数参与免疫调节的基因(如 Foxp3、IL-4、IL-10 和 IFN-g)的 CpG 位点的甲基化改变有关(例如,在研究前一个月,PM 暴露量增加与 IL-4 CpG24 位点的甲基化独立相关(估计值=0.16;P=0.0095)。此外,T 辅助免疫细胞类型(Th1、Th2 和 Th17)与 PM、O 和 CO 的短期暴露有关(例如,Th1 细胞与 30 天的 PM 有关:估计值=-0.34,P<0.0001)。B 细胞(估计值=-0.19)和 CD4+细胞(估计值=0.16)与 1 天的 NO2 暴露有关(P≤0.031),而 CD4+和 CD8+细胞与慢性暴露于多环芳烃(PAH)、NOx 和/或 NO 有关(所有 P≤0.038)。最后,舒张压(DBP)与 CO 和 PAH 的长期暴露呈负相关,收缩压和脉搏压与短期 NO 和慢性 NOx 暴露有关。我们的研究结果表明,大气污染暴露与免疫调节基因的甲基化、免疫细胞谱和血压之间存在关联,这表明即使在年幼时,免疫系统和心血管系统也会受到空气污染的负面影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1f/7893154/34253f0b4caf/41598_2021_83577_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1f/7893154/b9b280b10c09/41598_2021_83577_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1f/7893154/11d8cafa1ac4/41598_2021_83577_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1f/7893154/34253f0b4caf/41598_2021_83577_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1f/7893154/b9b280b10c09/41598_2021_83577_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1f/7893154/11d8cafa1ac4/41598_2021_83577_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1f/7893154/34253f0b4caf/41598_2021_83577_Fig3_HTML.jpg

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