Aberrant expression of FoxP3 in a human T�cell line possessing regulatory T cell‑like function and exposed continuously to asbestos fibers

Abstract

Prompted by the known carcinogenic activity of asbestos, our investigations revealed that asbestos causes a reduction in antitumor immunity. One mechanism involves the enhancement of regulatory T (Treg) cell function and volume assayed using MT‑2 original cells (Org), an HTLV‑1 immortalized human T cell line which possesses Treg‑like function. Continuous and relatively low‑dose exposure of MT‑2 to asbestos fibers yielded sublines resistant to asbestos‑induced apoptosis and enhanced Treg function via cell‑cell contact mechanisms and increased the production of soluble factors such as interleukin (IL)‑10 and transforming growth factor (TGF)‑β. Additionally, cell cycle progression was accelerated in these sublines. Subsequently, the status of the Treg‑specific transcription factor FoxP3 was examined. Unexpectedly, FoxP3 mRNA levels decreased in the sublines, although significant changes in protein expression were absent. Methylation analysis of CpG sites located in the promoter region of FoxP3 in original MT‑2 cells and sublines showed almost complete methylation in Org and slight hypomethylation in the sublines. Although treatment with the demethylating agent 5‑aza‑deoxycytidine tended to upregulate FoxP3 expression, the methylation status did not match the mRNA expression and enhanced function. Additionally, the expression of other transcription factors related to Treg did not differ between Org and subline CB1. Collectively, aberrant expression and methylation patterns of FoxP3 were detected in human T cells continuously exposed to asbestos, although cell function was enhanced by asbestos exposure. Future analyses to identify factors responsible for Treg functional enhancements induced by asbestos, such as the investigation of surface molecules, are needed for the development of strategies to prevent the occurrence of asbestos‑induced cancers.

The regulatory effect of Lactobacillus rhamnosus GG on T lymphocyte and the development of intestinal villi in piglets of different periods

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The hypermethylation of FOXP3 gene as an epigenetic marker for the identification of arsenic poisoning risk

“…9 Thus, we suggest that FOXP3 methylation has the potential to be a biomarker for assessment of arsenic poisoning. Additionally, the literature revealed that the aberrant DNA methylation of FOXP3 was a sensitive marker of environmental pollutants such as black carbon, 26 PM 2.5 27 , tobacco smoke, 28 and asbestos fibers, 29 and was involved in lung dysfunction or asthma caused by these pollutants through the disruption of immunosuppressive function and homeostasis of pro/anti-inflammatory. These findings added to the evidences that aberrant FOXP3 methylation may be a universal marker for the risk assessment of environmental exposure-induced inflammation-based health threats.…”

The Importance of the Transcription Factor Foxp3 in the Development of Primary Immunodeficiencies

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