PKC-Θ is an Important Driver of Fluoride-Induced Immune Imbalance of Regulatory T Cells/Effector T Cells

56 Pages Posted: 13 Feb 2024

See all articles by Siqi Zhu

Siqi Zhu

Harbin Medical University

Bingshu Liu

Harbin Medical University

Guiyu Fu

Harbin Medical University

Liu Yang

Harbin Medical University

Dan Wei

Harbin Medical University

Liwei Zhang

Harbin Medical University

Qiong Zhang

Harbin Medical University

Yanhui Gao

Harbin Medical University

Dianjun Sun

Chinese Center for Disease Control and Prevention (China CDC) - Center for Endemic Disease Control

Wei Wei

Harbin Medical University

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.

Note:
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

Suggested Citation

Zhu, Siqi and Liu, Bingshu and Fu, Guiyu and Yang, Liu and Wei, Dan and Zhang, Liwei and Zhang, Qiong and Gao, Yanhui and Sun, Dianjun and Wei, Wei, PKC-Θ is an Important Driver of Fluoride-Induced Immune Imbalance of Regulatory T Cells/Effector T Cells. Available at SSRN: https://ssrn.com/abstract=4717811 or http://dx.doi.org/10.2139/ssrn.4717811

Siqi Zhu

Harbin Medical University ( email )

157 Baojian Rd
Nangang Qu
Haerbin Shi
China

Bingshu Liu

Harbin Medical University ( email )

157 Baojian Rd
Nangang Qu
Haerbin Shi
China

Guiyu Fu

Harbin Medical University ( email )

157 Baojian Rd
Nangang Qu
Haerbin Shi
China

Liu Yang

Harbin Medical University ( email )

157 Baojian Rd
Nangang Qu
Haerbin Shi
China

Dan Wei

Harbin Medical University ( email )

157 Baojian Rd
Nangang Qu
Haerbin Shi
China

Liwei Zhang

Harbin Medical University ( email )

157 Baojian Rd
Nangang Qu
Haerbin Shi
China

Qiong Zhang

Harbin Medical University ( email )

157 Baojian Rd
Nangang Qu
Haerbin Shi
China

Yanhui Gao

Harbin Medical University ( email )

157 Baojian Rd
Nangang Qu
Haerbin Shi
China

Dianjun Sun

Chinese Center for Disease Control and Prevention (China CDC) - Center for Endemic Disease Control ( email )

Harbin
China

Wei Wei (Contact Author)

Harbin Medical University ( email )

157 Baojian Rd
Nangang Qu
Haerbin Shi
China

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