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Age-Related Changes in DNA Methylation Associated with Shifting Th1/Th2 Balance

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Abstract

This study was conducted in order to explore age-related changes in the production of Th1 and Th2 cytokines and determine the corresponding status of DNA methylation. The plasma IL-4 and IFN-γ levels and expression of Th-related cytokines and transcription factors in CD4+ splenocytes were observed in mice at different weeks of age. The DNA methylation levels of IL-4 and IFN-γ promoters and the related regulatory regions in CD4+ splenocytes of mice at different weeks of age were analyzed. The DNA methyltransferase (DNMT) levels in CD4+ splenocytes of mice were analyzed. Changes in plasma IL-4 and IFN-γ levels after 5-AZA injection were evaluated. Plasma IL-4 and IL-4 expression in CD4+ splenocytes declined with increasing age, while the IFN-γ expression levels increased. Th-related transcription factors showed no differences in mice at different weeks of age. The DNMT1 and DNMT3b mRNA expression did not show significant changes in CD4+ splenocytes, whereas the DNMT3a mRNA expression increased with age. DNA methylation in the IL-4 promoter was increased, while DNA methylation in the IFN-γ promoter was decreased. The methylation of RSH7, CNS-1, and HSV increased significantly with age. Age-related changes in DNA methylation may be associated with the shift in Th1/Th2 balance.

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Acknowledgments

We thank Dr. Pengqiang Wen, a member of Pediatric Institution of Shenzhen Children’s Hospital, for sharing useful references on the topic.

Authors’ Contributions

Qiu Li and Chengrong Li contributed to the conception of the study. Guobin Wang and Jun Yang contributed significantly to the analysis and manuscript preparation; Yu Xia performed the data analyses and wrote the manuscript.

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Authors and Affiliations

  1. Department of Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, China

    Yu Xia & Qiu Li

  2. Department of Immunology, Shenzhen Children’s Hospital, Shenzhen, 518026, Guangdong, China

    Jun Yang, Guobin Wang & Chengrong Li

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  1. Yu Xia
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  2. Jun Yang
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Correspondence to Chengrong Li or Qiu Li.

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ELECTRONIC SUPPLEMENTARY MATERIAL

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Supplementary Fig. 1

The Mean Fluorescence Intensities (MFIs) of IL-4 and IFN-γ in the plasma of mice with different week age. A MFIs of IL-4 in the plasma of mice with different week age B MFIs of IFN-γ in the plasma of mice with different week age. (GIF 28 kb)

High resolution image (TIF 1,216 kb)

Supplementary Fig. 2

The MFIs of IL-4 in the plasma of mice with 4-week age before and after 5-AZA administration. A. MFIs of IL-4 in the plasma of normal 4-week-old mice; B. Increased MFIs of IL-4 in the plasma of 4-week-old mice after 5-AZA administration; C. Unchanged MFIs of IL-4 in the plasma of 4-week-old mice after 5-AZA administration; D. Unchanged MFIs of IL-4 in the plasma of 4-week-old mice after 5-AZA administration. (GIF 25 kb)

High resolution image (TIF 595 kb)

Supplementary Fig. 3

The MFIs of IFN-γ in the plasma of mice with 7-week age before and after 5-AZA Administration. A. MFIs of IFN-γ in the plasma of normal 7-week-old mice; B. Increased MFIs of IFN-γ in the plasma of 7-week-old mice after 5-AZA administration; C. Decreased MFIs of IFN-γ in the plasma of 7-week-old mice after 5-AZA administration; D. Increased MFIs of IFN-γ in the plasma of 7-week-old mice after 5-AZA administration. (GIF 22 kb)

High resolution image (TIF 507 kb)

Supplementary Table 1

Sequence of Primers in PCR. (DOC 38 kb)

Supplementary Table 2

Sequence of Primers in MSP and Ms-SNuPE. (DOC 39 kb)

Supplementary Table 3

mRNA Expression of Th Related Genes in CD4+ Splenocytes from Mice with Different Week Age (DOC 43 kb)

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Xia, Y., Yang, J., Wang, G. et al. Age-Related Changes in DNA Methylation Associated with Shifting Th1/Th2 Balance. Inflammation 39, 1892–1903 (2016). https://doi.org/10.1007/s10753-016-0425-0

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  • DOI: https://doi.org/10.1007/s10753-016-0425-0

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