Department of Pharmaceutical Sciences, University of New Mexico College of Pharmacy, Albuquerque, NM, United States of America.
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, United States of America.
PLoS One. 2019 Jul 31;14(7):e0220451. doi: 10.1371/journal.pone.0220451. eCollection 2019.
Exposures to environmental arsenic (As) and polycyclic aromatic hydrocarbons (PAH) have been shown to independently cause dysregulation of immune function. Little data exists on the associations between combined exposures to As and PAH with immunotoxicity in humans. In this work we examined associations between As and PAH exposures with lymphoid cell populations in human peripheral blood mononuclear cells (PBMC), as well as alterations in differentiation and activation of B and T cells. Two hundred men, participating in the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh, were selected for the present study based on their exposure to As from drinking water and their cigarette smoking status. Blood and urine samples were collected from study participants. We utilized multiparameter flow cytometry in PBMC to identify immune cells (B, T, monocytes, NK) as well as the T-helper (Th) cell subsets (Th1, Th2, Th17, and Tregs) following ex vivo activation. We did not find evidence of interactions between As and PAH exposures. However, individual exposures (As or PAH) were associated with changes to immune cell populations, including Th cell subsets. Arsenic exposure was associated with an increase in the percentage of Th cells, and dose dependent changes in monocytes, NKT cells and a monocyte subset. Within the Th cell subset we found that Arsenic exposure was also associated with a significant increase in the percentage of circulating proinflammatory Th17 cells. PAH exposure was associated with changes in T cells, monocytes and T memory (Tmem) cells and with changes in Th, Th1, Th2 and Th17 subsets all of which were non-monotonic (dose dependent). Alterations of immune cell populations caused by environmental exposures to As and PAH may result in adverse health outcomes, such as changes in systemic inflammation, immune suppression, or autoimmunity.
暴露于环境砷（As）和多环芳烃（PAH）已被证明会独立导致免疫功能失调。关于 As 和 PAH 联合暴露与人类免疫毒性之间的关联，数据很少。在这项工作中，我们研究了 As 和 PAH 暴露与人类外周血单个核细胞（PBMC）中淋巴样细胞群之间的关联，以及 B 和 T 细胞分化和激活的改变。在孟加拉国进行的砷纵向研究（HEALS）中，根据他们饮用水中的砷暴露和吸烟状况，从 200 名男性中选择了本研究的参与者。从研究参与者中采集了血液和尿液样本。我们利用 PBMC 中的多参数流式细胞术来识别免疫细胞（B、T、单核细胞、NK）以及 T 辅助（Th）细胞亚群（Th1、Th2、Th17 和 Tregs）在体外激活后。我们没有发现 As 和 PAH 暴露之间存在相互作用的证据。然而，个体暴露（As 或 PAH）与免疫细胞群体的变化有关，包括 Th 细胞亚群。砷暴露与 Th 细胞百分比的增加以及单核细胞、NKT 细胞和单核细胞亚群的剂量依赖性变化有关。在 Th 细胞亚群中，我们发现砷暴露也与循环前炎性 Th17 细胞百分比的显著增加有关。PAH 暴露与 T 细胞、单核细胞和 T 记忆（Tmem）细胞的变化以及 Th、Th1、Th2 和 Th17 亚群的变化有关，所有这些变化都是非线性的（剂量依赖性的）。环境暴露于 As 和 PAH 引起的免疫细胞群体的改变可能导致不良的健康后果，例如系统性炎症、免疫抑制或自身免疫的改变。
