Modulation and the Underlying Mechanism of T Cells in Thymus of Mice by Oral Administration of Sodium Fluoride

Abstract

The underlying mechanism of thymic T cell regulation has been a hot topic of research in recent years. Fluoride is toxic at high concentrations and fluoride toxicity to thymic T cells was assessed in our study. To explore T cell responses to excess fluoride, different concentrations of fluoride were uptake by mice for 6 weeks. The expression of genes, including Foxn1, Cbx4, DLL4, and IL-7 gene, associated with the development and differentiation of T cells in thymic epithelial cells(TECs) was lower in the experimental groups than that in the control group. The percentages of CD4(+) and CD8(+) T cells that decreased with the fluoride administration were confirmed by flow cytometry. The mRNA levels of immunoregulatory cytokines IL-2 and IL-10, which participate in T cell proliferation, also declined in the experimental groups as compared with the control group. Expression of the T cell function-related genes CD2, PTPRC, CD69, and CD101, which are involved in thymic function in mice, decreased with the fluoride administration. Our findings suggest that the administration of high concentrations of fluoride to mice induces a decrease in CD4(+) and CD8(+) thymus T cells by harming TECs leading to the dysfunction of the thymus by altering the expression of T cell function-related genes and immunoregulatory cytokine production.

Effects of sodium fluoride on blood cellular and humoral immunity in mice

“…In our previous study, we found that high fluoride levels can reduce IL-2, IL-4, IL-6, TNF-α and IFN-γ in the cecal tonsil, and intestines of broiler chickens [ 14 ], and that NaF can reduce the percentages of CD3 + , CD3 + CD4 + , CD3 + CD8 + T lymphocytes and CD19 + B lymphocytes and of IL-2, TNF-α, IFN-γ, TGF-β expression levels in cultured splenic lymphocytes of mice [ 36 ]. Our findings are consistent with the report of Yin et al [ 43 ] that high fluoride decreased the percentages of thymic CD4 + , CD8 + T cells and IL-2, IL-10 mRNA expression in mice. Also, Fentue et al [ 19 ] reported that NaF decreased IL-10 mRNA expression level in murine macrophages.…”

Comparative Transcriptomics Reveals the Role of the Toll-Like Receptor Signaling Pathway in Fluoride-Induced Cardiotoxicity

“…It has been reported that NaF can suppress the cellular immunity in mice and Th2 cytokines, including IL-4, IL-6, and IL-10, and Th17 cytokine (IL-17A) contents were decreased after exposed to NaF in excess of 12 mg/kg. 31 In addition, our findings are consistent with some reports that high fluoride decreased the percentages of thymic CD4+ and CD8+T cells and IL-2 and IL-10 mRNA expression in mice, 35 and at the cellular level, high NaF concentrations (20 and 50 mg/L) significantly reduced the secretion of TNFα, IL-2, IL-6, and IL-1β in the supernatant. 33 Therefore, we speculate that NaF affects the inflammation and immune response of rat heart tissue by affecting factors such as IL-6 and IL-10.…”

Progress in research on the role of fluoride in immune damage

“…Fluoride induces the apoptosis of thymus cells and leads to immunosuppression; additionally, high concentrations of fluoride damages thymic epithelial cells (TECs) by altering the expression of T cell function–related genes and the production of immunomodulatory cytokines ( 45 ). In TECs, the expression of the Foxn1 , Cbx4 , DLL4 , and IL-7 genes related to T cell development and differentiation are reduced ( 46 ).…”