PKC-θ is an important driver of fluoride-induced immune imbalance of regulatory T cells/effector T cells.

Fluoride is unnecessary in the human body. Long-term fluoride exposure may lead to immune system abnormalities. However, the mechanism remains unclear. This study aim to explore the mechanism of fluoride interference in the immune system and also identify the key indicators of fluoride-induced immune damage. Questionnaires were used to collect basic information. Multiple linear analyses and other statistical methods were used in order to process the data. Flow cytometry was used to detect relevant immunomarkers and analyze immune damage. Simultaneously, Wistar rats and cell models exposed to fluoride were established to detect the effects of fluoride on immune homeostasis. The results showed that sex, residence time, smoking, and Corona Virus Disease 2019 (COVID-19) infection may indirectly influence fluoride-induced immune damage. In residents of fluoride-exposed areas, there was a significant decrease in CD3 ⁺ T lymphocytes and CD4 ⁺ and CD8 ⁺ cells and a downward trend in the CD4 ⁺ /CD8 ⁺ cell ratio. CD4 ⁺ CD8 ⁺ /CD4 ⁺ , regulatory T cells (Tregs), and Tregs/effector T cells (Teffs) ratios showed opposite changes. Fluoride 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. This study represents the first evidence suggesting that PKC-θ may be the key to immune imbalance in the body under fluoride exposure. It is possible that Tregs/Teffs cell ratio provide a reference point for the diagnosis and treatment of fluoride-induced immune damage.
Competing Interests: Declaration of competing interest The author declares that he does not receive any payment from any source and that there is no conflict of interest with the content of this article. The author's unit is shown on the cover. The preparation of this review was carried out during the author's normal working hours. This manuscript was written entirely by the author, who is solely responsible for the preparation of this manuscript. The views and conclusions expressed therein are those of the author and are not necessarily those of any sponsoring entity. None of the authors have been previously involved in any litigation, advocacy, or regulatory activity related to the content of this paper.
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