Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women

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Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. / Engström, Karin; Wojdacz, Tomasz K.; Marabita, Francesco; Ewels, Philip; Käller, Max; Vezzi, Francesco; Prezza, Nicola; Gruselius, Joel; Vahter, Marie; Broberg, Karin.

In: Archives of Toxicology, Vol. 91, No. 5, 2017, p. 2067-2078.

Research output: Contribution to journalArticle

Harvard

Engström, K, Wojdacz, TK, Marabita, F, Ewels, P, Käller, M, Vezzi, F, Prezza, N, Gruselius, J, Vahter, M & Broberg, K 2017, 'Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women', Archives of Toxicology, vol. 91, no. 5, pp. 2067-2078. https://doi.org/10.1007/s00204-016-1879-4

APA

Engström, K., Wojdacz, T. K., Marabita, F., Ewels, P., Käller, M., Vezzi, F., ... Broberg, K. (2017). Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. Archives of Toxicology, 91(5), 2067-2078. https://doi.org/10.1007/s00204-016-1879-4

CBE

Engström K, Wojdacz TK, Marabita F, Ewels P, Käller M, Vezzi F, Prezza N, Gruselius J, Vahter M, Broberg K. 2017. Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. Archives of Toxicology. 91(5):2067-2078. https://doi.org/10.1007/s00204-016-1879-4

MLA

Vancouver

Author

Engström, Karin ; Wojdacz, Tomasz K. ; Marabita, Francesco ; Ewels, Philip ; Käller, Max ; Vezzi, Francesco ; Prezza, Nicola ; Gruselius, Joel ; Vahter, Marie ; Broberg, Karin. / Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. In: Archives of Toxicology. 2017 ; Vol. 91, No. 5. pp. 2067-2078.

RIS

TY - JOUR

T1 - Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women

AU - Engström, Karin

AU - Wojdacz, Tomasz K.

AU - Marabita, Francesco

AU - Ewels, Philip

AU - Käller, Max

AU - Vezzi, Francesco

AU - Prezza, Nicola

AU - Gruselius, Joel

AU - Vahter, Marie

AU - Broberg, Karin

PY - 2017

Y1 - 2017

N2 - Arsenic, a carcinogen with immunotoxic effects, is a common contaminant of drinking water and certain food worldwide. We hypothesized that chronic arsenic exposure alters gene expression, potentially by altering DNA methylation of genes encoding central components of the immune system. We therefore analyzed the transcriptomes (by RNA sequencing) and methylomes (by target-enrichment next-generation sequencing) of primary CD4-positive T cells from matched groups of four women each in the Argentinean Andes, with fivefold differences in urinary arsenic concentrations (median concentrations of urinary arsenic in the lower- and high-arsenic groups: 65 and 276 μg/l, respectively). Arsenic exposure was associated with genome-wide alterations of gene expression; principal component analysis indicated that the exposure explained 53% of the variance in gene expression among the top variable genes and 19% of 28,351 genes were differentially expressed (false discovery rate <0.05) between the exposure groups. Key genes regulating the immune system, such as tumor necrosis factor alpha and interferon gamma, as well as genes related to the NF-kappa-beta complex, were significantly downregulated in the high-arsenic group. Arsenic exposure was associated with genome-wide DNA methylation; the high-arsenic group had 3% points higher genome-wide full methylation (>80% methylation) than the lower-arsenic group. Differentially methylated regions that were hyper-methylated in the high-arsenic group showed enrichment for immune-related gene ontologies that constitute the basic functions of CD4-positive T cells, such as isotype switching and lymphocyte activation and differentiation. In conclusion, chronic arsenic exposure from drinking water was related to changes in the transcriptome and methylome of CD4-positive T cells, both genome wide and in specific genes, supporting the hypothesis that arsenic causes immunotoxicity by interfering with gene expression and regulation.

AB - Arsenic, a carcinogen with immunotoxic effects, is a common contaminant of drinking water and certain food worldwide. We hypothesized that chronic arsenic exposure alters gene expression, potentially by altering DNA methylation of genes encoding central components of the immune system. We therefore analyzed the transcriptomes (by RNA sequencing) and methylomes (by target-enrichment next-generation sequencing) of primary CD4-positive T cells from matched groups of four women each in the Argentinean Andes, with fivefold differences in urinary arsenic concentrations (median concentrations of urinary arsenic in the lower- and high-arsenic groups: 65 and 276 μg/l, respectively). Arsenic exposure was associated with genome-wide alterations of gene expression; principal component analysis indicated that the exposure explained 53% of the variance in gene expression among the top variable genes and 19% of 28,351 genes were differentially expressed (false discovery rate <0.05) between the exposure groups. Key genes regulating the immune system, such as tumor necrosis factor alpha and interferon gamma, as well as genes related to the NF-kappa-beta complex, were significantly downregulated in the high-arsenic group. Arsenic exposure was associated with genome-wide DNA methylation; the high-arsenic group had 3% points higher genome-wide full methylation (>80% methylation) than the lower-arsenic group. Differentially methylated regions that were hyper-methylated in the high-arsenic group showed enrichment for immune-related gene ontologies that constitute the basic functions of CD4-positive T cells, such as isotype switching and lymphocyte activation and differentiation. In conclusion, chronic arsenic exposure from drinking water was related to changes in the transcriptome and methylome of CD4-positive T cells, both genome wide and in specific genes, supporting the hypothesis that arsenic causes immunotoxicity by interfering with gene expression and regulation.

KW - Arsenic

KW - CD4 cells

KW - Immune system

KW - Immunotoxic

KW - Methylomics

KW - Transcriptomics

UR - http://www.scopus.com/inward/record.url?scp=84994742990&partnerID=8YFLogxK

U2 - 10.1007/s00204-016-1879-4

DO - 10.1007/s00204-016-1879-4

M3 - Article

VL - 91

SP - 2067

EP - 2078

JO - Archiv fur Toxikologie

T2 - Archiv fur Toxikologie

JF - Archiv fur Toxikologie

SN - 0003-9446

IS - 5

ER -