Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction, The Fifth Affiliated Hospital of Jinan University (Heyuan Shenhe People's Hospital), Jinan University, Heyuan 517000, China; Department of Hematology, First Affiliated Hospital of Jinan University, Guangzhou 510632, China; Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, Jinan University, Guangzhou 510632, China.
Department of Clinical Laboratory, First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
J Hazard Mater. 2024 Dec 5;480:136096. doi: 10.1016/j.jhazmat.2024.136096. Epub 2024 Oct 9.
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.
三氯生（TCC）是一种广泛应用的环境内分泌干扰化学物质（EDC）。与大多数 EDC 类似，TCC 可能会损害各种物种的免疫力。然而，TCC 是否以及如何影响哺乳动物的适应性免疫仍未确定。在此，我们发现 TCC 会破坏原代人外周血样本、纯化的 CD8 T 细胞以及体内小鼠 CD8 T 细胞的激活和分化。在机制上，TCC 可能会阻断维生素 D 受体（VDR）的激活，并减少胆固醇的合成，胆固醇是维生素 D 的前体，因此由于 TCC 对其配体和受体本身的抑制，会抑制 VDR 信号转导。我们的研究结果阐明了 TCC 在哺乳动物适应性免疫中的危害和潜在机制，并强调了 VDR 作为 TCC 引起免疫缺陷的潜在治疗靶点。
