Triclocarban disrupts the activation and differentiation of human CD8+ T cells by suppressing the vitamin D receptor signaling

• Published in: Journal of hazardous materials 2024-12, Vol.480, p.136096, Article 136096
• Main Authors: Zhang, Yikai, Guo, Jiafan, Chen, Zhixi, Chang, Yiming, Zhang, Xingwei, Liu, Zirui, Li, Xinye, Zha, Xianfeng, Sun, Guodong, Li, Yangqiu
• Format: Article
• Language: English
• Subjects: Animals; Carbanilides - pharmacology; Carbanilides - toxicity; CD8+ T cell activation; CD8+ T cell differentiation; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell Differentiation - drug effects; Cells, Cultured; Endocrine Disruptors - toxicity; Female; Humans; Lymphocyte Activation - drug effects; Male; Mice; Mice, Inbred C57BL; Receptors, Calcitriol - metabolism; Signal Transduction - drug effects; Triclocarban; Vitamin D receptor
• ISSN: 0304-3894; 1873-3336; 1873-3336
• DOI: 10.1016/j.jhazmat.2024.136096

Triclocarban (TCC) is a widely applied environmental endocrine-disrupting chemical (EDC). Similar to most of EDCs, TCC potentially damages the immunity of various species. However, whether and how TCC impacts the adaptive immunity in mammals has yet to be determined. Herein, we discovered that TCC disrupts the activation and differentiation of CD8+ T cells in primary human peripheral blood samples, purified CD8+ T cells, and in mice in vivo. Mechanistically, TCC might block the activation of the vitamin D receptor (VDR) and reduce the synthesis of cholesterol, a precursor of vitamin D, resulting in inhibition of VDR signaling due to the suppression of both its ligand and the receptor itself by TCC. Our findings elucidate the hazard and potential mechanisms of TCC in mammalian adaptive immunity and highlighted VDR as a potential therapeutic target for the immunodeficiency caused by TCC. [Display omitted] •Triclocarban disrupts mammalian CD8+ T cells in vitro and in vivo.•Triclocarban suppresses the activation of vitamin D receptor.•Triclocarban decreases the synthesis of vitamin D precursor.