近日，大湾区城市环境安全与绿色发展教育部重点实验室学术骨干栾天罡教授团队博士后李心砚在环境领域著名学术期刊Environmental Science & Technology上发表了题为“Chlorinated Polycyclic Aromatic Hydrocarbons Induce Immunosuppression in THP-1 Macrophages Characterized by Disrupted Amino Acid Metabolism”的学术论文。本研究整合了高通量多靶点免疫毒性检测与非靶向代谢组学技术，联合评估了氯代多环芳烃的免疫毒性并探究了免疫代谢机制。研究首次证明了氯代多环芳烃在不激活AhR的较低浓度下（1 μM）能诱导免疫毒性，并讨论了巨噬细胞代谢过程在Cl-PAHs/PPAHs诱导免疫反应中的作用，为开发基于免疫代谢机制的环境化学品风险评估新方法提供了有力支持。

    论文DOI：https://doi.org/10.1021/acs.est.2c06471

氯代多环芳烃（Cl-PAHs）是一种新型的持久性有机污染物，具有一定的生物积累性和远距离传输能力，其主要来源是汽车尾气排放、垃圾焚烧以及电子垃圾拆解过程等。Cl-PAHs目前已报道在多种环境介质甚至生物样本中广泛存在，最新研究证实其在人体血液的暴露证据，因此对Cl-PAHs暴露风险和毒性研究十分迫切且必须。尽管PAHs的毒性研究已持续多年，然而对其氯代产物的健康风险评价却仍处于起步阶段，目前主要围绕芳香烃受体效应 (AhR effects) 展开。研究发现部分低芳环数的Cl-PAHs能引起比母体多环芳烃 (PPAHs) 更强烈的AhR效应，具有类二噁英的毒性。考虑到免疫系统是二噁英类物质攻击的敏感靶点，暗示氯代多环芳烃具有潜在的免疫毒性，但缺乏直接证据。本研究使用高内涵筛选系统，采用自主研发的基于 THP-1 巨噬细胞免疫功能的高通量多靶点检测方法，评估了Cl-PAHs和对应PPAHs对THP-1巨噬细胞的免疫毒性。结果发现Cl-PAHs表现出明显的免疫抑制毒性，而PPAHs则表现为不同的免疫干扰。在此基础上，通过对非靶向代谢组学与免疫表型结果进行多重相关性分析，发现氨基酸代谢异常很可能是导致Cl-PAHs及其母体化合物诱导免疫毒性的原因。

英文摘要：

Frequent chlorinated polycyclic aromatic hydrocarbon (Cl-PAH) occurrence in environmental samples and emerging detection in human serum have warned of their underestimated risks. Studies showed that some Cl-PAHs exhibit dioxin-like properties, implying immunotoxic potential but lacking direct evidence and specific mechanisms. Here, we integrated a high-content screening (HCS) system and high-resolution mass spectrometry to investigate the immune dysfunction and metabolic disruption induced by Cl-PAHs and their parent PAHs (PPAHs) in THP-1 macrophages. Both 9-chloroanthracene and 2,7-dichlorofluorene exerted clear immunosuppression on THP-1 mφs, while their PPAHs exhibited different immune disturbances. Interestingly, Cl-PAH/PPAHs induced complex alterations in the multicytokine/chemokine network, including biphasic alterations with initial inhibition and later enhancement. Furthermore, the protein–protein interaction results revealed that inflammatory cytokines are the core of this complicated network regulation. Connecting immune phenotypes and metabolomics, amino acid metabolism reprogramming was identified as a potential cause of Cl-PAH/PAH-induced immunotoxicity. Phytosphingosine and l-kynurenine were proposed as candidate immunosuppression biomarkers upon Cl-PAH exposure. This article provides direct immunotoxicity evidence of Cl-PAHs without activating AhR for the first time and discusses the contribution of metabolites to Cl-PAH/PPAH-induced immune responses in macrophages, highlighting the potential of developing new methods based on immunometabolism mechanisms for toxic risk evaluation of environmental chemicals.