Chronic Exposure to Water Pollutant Trichloroethylene Increased Epigenetic Drift in CD4⁺ T cells

Abstract

Aim: Autoimmune disease and CD4⁺ T-cell alterations are induced in mice exposed to the water pollutant trichloroethylene (TCE). We examined here whether TCE altered gene-specific DNA methylation in CD4⁺ T cells as a possible mechanism of immunotoxicity. Materials & methods: Naive and effector/memory CD4⁺ T cells from mice exposed to TCE (0.5 mg/ml in drinking water) for 40 weeks were examined by bisulfite next-generation DNA sequencing. Results: A probabilistic model calculated from multiple genes showed that TCE decreased methylation control in CD4⁺ T cells. Data from individual genes fitted to a quadratic regression model showed that TCE increased gene-specific methylation variance in both CD4 subsets. Conclusion: TCE increased epigenetic drift of specific CpG sites in CD4⁺ T cells.

Keywords::

• autoimmunity
• CD4⁺ T cells
• DNA methylation
• IFN-γ
• immunotoxicity
• next generation sequencing
• quadratic regression
• trichloroethylene

Acknowledgements

The authors are thankful to R Lee and D Barnette for excellent technical assistance.

Financial & competing interests disclosure

This work was supported by grants from the Arkansas Biosciences Institute, the NIH (R01ES017286, R01ES021484), the Organic Compounds Property Contamination class action settlement (CV 1992-002603) and the UAMS Translational Research Institute (NIH UL1RR029884). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by grants from the Arkansas Biosciences Institute, the NIH (R01ES017286, R01ES021484), the Organic Compounds Property Contamination class action settlement (CV 1992-002603) and the UAMS Translational Research Institute (NIH UL1RR029884). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.