PKC-Θ is an Important Driver of Fluoride-Induced Immune Imbalance of Regulatory T Cells/Effector T Cells
56 Pages Posted: 13 Feb 2024
Abstract
Fluoride is unnecessary in the human body. Long-term fluoride exposure may lead to immune system abnormalities; however, the mechanism remains unclear. Through epidemiological investigation and detection of immune targets, we observed a significant decrease in CD3+ T lymphocytes and CD4+ and CD8+ cells in residents of fluorine-exposed areas, and a downward trend in the CD4+/CD8+ cell ratio. CD4+CD8+/CD4+, regulatory T cell (Treg), and Tregs/effector T cell (Teff) ratios showed opposite changes. Sex, residence time, smoking, and COVID-19 infection may indirectly aggravate fluoride-induced immune damage. To our best knowledge, this is the first report on that fluorine inhibits T cell activation by inhibiting the expression and phosphorylation of Protein Kinase C-θ (PKC-θ), hinders the internalization of T cell receptors, and affects NF-kB and c-Jun protein expression, leading to homeostatic Treg/Teff imbalance in vivo and in vitro experiments. In conclusion, fluorine interferes with human immune cell subsets by changing PKC-θ expression, and enhances Tregs inhibition of Teffs. PKC-θ may be the key to immune imbalance in the body under fluoride exposure.
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Funding declaration: This work was supported by the National Natural Science Foundation of China (Nos. 81972984 and 82373699), the National Key R&D Program of China (2022YFC2503000), and the Natural Science Foundation of Heilongjiang Province684 Joint Guidance (LH2021H009).
Conflict of Interests: None.
Ethical Approval: This study was approved by the Ethics Review Committee of the Chinese Center for Disease Control and Prevention, and all participants provided written informed consent. All experiments and related procedures involving the use of animals were approved by the Institutional Animal Protection and Use Committee of Harbin Medical University.
Keywords: Protein Kinase C-θ, Fluoride, T lymphocytes, Regulatory T cells, homeostasis imbalance
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