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Tobacco smoking differently influences cell types of the innate and adaptive immune system—indications from CpG site methylation

BACKGROUND: Tobacco smoke is worldwide one of the main preventable lifestyle inhalative pollutants causing severe adverse health effects. Epidemiological studies revealed association of tobacco smoking with epigenetic changes at single CpGs in blood. However, the biological relevance of the often on...

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Autores principales: Bauer, Mario, Fink, Beate, Thürmann, Loreen, Eszlinger, Markus, Herberth, Gunda, Lehmann, Irina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973040/
https://www.ncbi.nlm.nih.gov/pubmed/27493699
http://dx.doi.org/10.1186/s13148-016-0249-7
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author Bauer, Mario
Fink, Beate
Thürmann, Loreen
Eszlinger, Markus
Herberth, Gunda
Lehmann, Irina
author_facet Bauer, Mario
Fink, Beate
Thürmann, Loreen
Eszlinger, Markus
Herberth, Gunda
Lehmann, Irina
author_sort Bauer, Mario
collection PubMed
description BACKGROUND: Tobacco smoke is worldwide one of the main preventable lifestyle inhalative pollutants causing severe adverse health effects. Epidemiological studies revealed association of tobacco smoking with epigenetic changes at single CpGs in blood. However, the biological relevance of the often only marginal methylation changes remains unclear. RESULTS: Comparing genome-wide changes in CpG methylation of three recently reported epidemiological datasets, two obtained on whole blood and one on peripheral blood mononuclear cells (PBMCs), it becomes evident that the majority of methylation changes (86.7 and 93.3 %) in whole blood account for changes in granulocytes. Analyzing, in more detail, seven highly significant reported smoking-induced methylation changes at single CpGs in different blood cell types of healthy volunteers (n = 32), we confirmatively found a strong cell-type specificity. Two CpGs in GFI1 and F2RL3 were significantly hypomethylated in granulocytes (−11.3 %, p = 0.001; −8.7 %, p = 0.001, respectively) but not in PBMCs of smokers while two CpGs in CPOX and GPR15 were found to be hypomethylated in PBMC (−4.3 %, p = 0.003; −4.2 %, P = 0.009, respectively) and their subtypes of GPR15 non-expressing (−3.2 %, p = 0.027; −2.5 %, p = 0.032, respectively) and smoking-evoked GPR15 expressing T cells (−15.8 %, p < 0.001; −13.8 %, p = 0.018, respectively) but not in granulocytes. In contrast, cg05575921 within AHRR was hypomethylated in every analyzed cell type of smokers, but with a different degree. Both, hypomethylation at cg05575921 in granulocytes (−55.2 % methylation change in smokers, p < 0.001) and the frequency of GPR15+ T cells (9.8–37.1 % in smokers), possessing a specific hypomethylation at cg19859270, were strongly associated with smoking behavior at individual level and could therefore serve as valuable biomarkers indicating a disturbed homeostasis in smokers. In contrast to the reported long-term persistent methylation changes in adult smokers after cessation, the hypomethylation at cg05575921 in prenatally tobacco smoke-exposed children (n = 13) from our LINA cohort was less stable and disappeared already within 2 years after birth. CONCLUSIONS: Studying cell type-specific methylation changes provides helpful information regarding the biological relevance of epigenetic modifications. Here, we could show that smoking differently affects both cells of the innate and adaptive immune systems. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-016-0249-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-49730402016-08-05 Tobacco smoking differently influences cell types of the innate and adaptive immune system—indications from CpG site methylation Bauer, Mario Fink, Beate Thürmann, Loreen Eszlinger, Markus Herberth, Gunda Lehmann, Irina Clin Epigenetics Research BACKGROUND: Tobacco smoke is worldwide one of the main preventable lifestyle inhalative pollutants causing severe adverse health effects. Epidemiological studies revealed association of tobacco smoking with epigenetic changes at single CpGs in blood. However, the biological relevance of the often only marginal methylation changes remains unclear. RESULTS: Comparing genome-wide changes in CpG methylation of three recently reported epidemiological datasets, two obtained on whole blood and one on peripheral blood mononuclear cells (PBMCs), it becomes evident that the majority of methylation changes (86.7 and 93.3 %) in whole blood account for changes in granulocytes. Analyzing, in more detail, seven highly significant reported smoking-induced methylation changes at single CpGs in different blood cell types of healthy volunteers (n = 32), we confirmatively found a strong cell-type specificity. Two CpGs in GFI1 and F2RL3 were significantly hypomethylated in granulocytes (−11.3 %, p = 0.001; −8.7 %, p = 0.001, respectively) but not in PBMCs of smokers while two CpGs in CPOX and GPR15 were found to be hypomethylated in PBMC (−4.3 %, p = 0.003; −4.2 %, P = 0.009, respectively) and their subtypes of GPR15 non-expressing (−3.2 %, p = 0.027; −2.5 %, p = 0.032, respectively) and smoking-evoked GPR15 expressing T cells (−15.8 %, p < 0.001; −13.8 %, p = 0.018, respectively) but not in granulocytes. In contrast, cg05575921 within AHRR was hypomethylated in every analyzed cell type of smokers, but with a different degree. Both, hypomethylation at cg05575921 in granulocytes (−55.2 % methylation change in smokers, p < 0.001) and the frequency of GPR15+ T cells (9.8–37.1 % in smokers), possessing a specific hypomethylation at cg19859270, were strongly associated with smoking behavior at individual level and could therefore serve as valuable biomarkers indicating a disturbed homeostasis in smokers. In contrast to the reported long-term persistent methylation changes in adult smokers after cessation, the hypomethylation at cg05575921 in prenatally tobacco smoke-exposed children (n = 13) from our LINA cohort was less stable and disappeared already within 2 years after birth. CONCLUSIONS: Studying cell type-specific methylation changes provides helpful information regarding the biological relevance of epigenetic modifications. Here, we could show that smoking differently affects both cells of the innate and adaptive immune systems. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-016-0249-7) contains supplementary material, which is available to authorized users. BioMed Central 2016-08-03 /pmc/articles/PMC4973040/ /pubmed/27493699 http://dx.doi.org/10.1186/s13148-016-0249-7 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bauer, Mario
Fink, Beate
Thürmann, Loreen
Eszlinger, Markus
Herberth, Gunda
Lehmann, Irina
Tobacco smoking differently influences cell types of the innate and adaptive immune system—indications from CpG site methylation
title Tobacco smoking differently influences cell types of the innate and adaptive immune system—indications from CpG site methylation
title_full Tobacco smoking differently influences cell types of the innate and adaptive immune system—indications from CpG site methylation
title_fullStr Tobacco smoking differently influences cell types of the innate and adaptive immune system—indications from CpG site methylation
title_full_unstemmed Tobacco smoking differently influences cell types of the innate and adaptive immune system—indications from CpG site methylation
title_short Tobacco smoking differently influences cell types of the innate and adaptive immune system—indications from CpG site methylation
title_sort tobacco smoking differently influences cell types of the innate and adaptive immune system—indications from cpg site methylation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973040/
https://www.ncbi.nlm.nih.gov/pubmed/27493699
http://dx.doi.org/10.1186/s13148-016-0249-7
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