双酚 A (BPA) 是一种有据可查的内分泌干扰化学物质，广泛用于塑料产品中。除了内分泌干扰作用外，BPA 还具有免疫毒性。由于双酚 A 对人类健康产生不利影响，许多国家已禁止使用。近年来，双酚B（BPB）、双酚E（BPE）、双酚S（BPS）、双酚芴（BHPF）等多种化学品已被用来替代BPA。由于这些替代化学品的化学结构与 BPA 相似，因此也可能危害人体健康。然而，它们的免疫毒性和毒性背后的分子机制仍然很大程度上未知。本研究的目的是通过将原代人淋巴细胞暴露于 BPA 及其替代化学品来研究 BPA 及其替代化学品的免疫毒性以及潜在机制。我们的结果表明，接触 BPA 及其替代化学物质会改变白细胞介素 (IL) 和细胞因子的产生，例如 IL-1b、IL-5、IL-6、IL-8、干扰素 alfa-2b (IFN-a2B) 和淋巴细胞中的肿瘤坏死因子α（TNF-α）。其中BPA和BHPF的抑制作用较大。通过比较转录组分析，我们进一步研究了 BHPF 暴露改变的生物过程和信号通路。我们的数据强调了通过基因簇的放松管制，人类淋巴细胞中免疫反应、T 细胞功能和细胞因子-细胞因子受体相互作用的改变。此外，Ingenuity Pathway分析结果证明了T淋巴细胞功能的抑制，包括分化、运动和浸润。我们的结果首次描述了 BHPF 对人类淋巴细胞免疫毒性的机制。版权所有 © 2024。由 Elsevier B.V. 出版。

Bisphenol A (BPA) is a well-documented endocrine-disrupting chemical widely used in plastic products. In addition to its endocrine-disrupting effects, BPA exhibits immunotoxicity. Many countries have banned BPA because of its adverse effects on human health. In recent years, many chemicals such as bisphenol B (BPB), bisphenol E (BPE), bisphenol S (BPS), and bisphenol fluorene (BHPF) have been used to replace BPA. Because these replacement chemicals have chemical structures similar to that of BPA, they may also harm human health. However, their immunotoxicity and the molecular mechanisms underlying their toxicity remain largely unknown. The aim of this study was to investigate the immunotoxicity of BPA and its replacement chemicals, as well as the underlying mechanisms by exposing primary human lymphocytes to BPA and its replacement chemicals. Our results showed that exposure to BPA and its replacement chemicals altered the interleukin (IL) and cytokine production, such as IL-1b, IL-5, IL-6, IL-8, interferon alfa-2b (IFN-a2B), and tumor necrosis factor alpha (TNF-α), in the lymphocytes. Among these, BPA and BHPF caused a greater inhibition. Using comparative transcriptomic analysis, we further investigated the biological processes and signaling pathways altered by BHPF exposure. Our data highlighted alterations in the immune response, T cell function, and cytokine-cytokine receptor interactions in human lymphocytes through the deregulation of gene clusters. In addition, the results of ingenuity pathway analysis demonstrated the inhibition of T lymphocyte function, including differentiation, movement, and infiltration. Our results, for the first time, delineate the mechanisms underlying the immunotoxicity of BHPF in human lymphocytes.Copyright © 2024. Published by Elsevier B.V.