Department of Pharmaceutical Sciences, University of New Mexico Health Sciences Center, Albuquerque, NM, United States.
Department of Pharmaceutical Sciences, University of New Mexico Health Sciences Center, Albuquerque, NM, United States.
Toxicol Appl Pharmacol. 2022 Nov 1;454:116233. doi: 10.1016/j.taap.2022.116233. Epub 2022 Sep 9.
Trichloroethylene (TCE) is a widely used industrial chemical and common environmental pollutant. Exposure to TCE promotes CD4 T cell-driven autoimmunity including autoimmune hepatitis (AIH) in both humans and female autoimmune-prone mice. Because the developing immune system is more sensitive during development, we predicted that non- autoimmune-prone, C57/Bl6 (B6) mice would exhibit some autoimmune-related changes using the Developmental Origins of Health and Disease (DOHaD) model of exposure. Both male and female mice were exposed to vehicle or an environmentally relevant dose of 5 μg/ml TCE (0.9 mg/kg/day) beginning at 2 weeks pre-conception and ending at weaning. CD4+ T cells were assessed for phenotypic markers by flow cytometry. An assessment of cytokines elicited ex vivo after 4d polarization from naïve to CD4 T helper subsets (i.e., Th1, Th17, and T reg) was conducted. mRNA expression of liver genes associated with inflammation, regeneration/repair associated with AIH disease progression in autoimmune-prone mice were evaluated by qRT-PCR. The results demonstrated TCE's ability to induce autoimmune- related biomarkers in B6 mice to an even greater degree in females compared to males when exposed during development.
三氯乙烯（TCE）是一种广泛使用的工业化学品和常见的环境污染物。暴露于 TCE 会促进 CD4 T 细胞驱动的自身免疫，包括人类和自身免疫倾向的雌性小鼠中的自身免疫性肝炎（AIH）。由于在发育过程中免疫系统发育得更敏感，我们预测使用健康与疾病的发育起源（DOHaD）模型的暴露，非自身免疫倾向的 C57/Bl6（B6）小鼠将表现出一些与自身免疫相关的变化。从受孕前 2 周开始，雄性和雌性小鼠均接受载体或环境相关剂量的 5μg/ml TCE（0.9mg/kg/天），直至断奶。通过流式细胞术评估 CD4+T 细胞的表型标记。对从幼稚 CD4 T 辅助细胞亚群（即 Th1、Th17 和 Treg）极化 4 天后体外诱发出的细胞因子进行评估。通过 qRT-PCR 评估与 AIH 疾病进展相关的炎症和再生/修复相关的肝脏基因在自身免疫倾向的小鼠中的 mRNA 表达。结果表明，与雄性相比，暴露于发育过程中的 TCE 甚至能够在雌性 B6 小鼠中诱导出更严重的自身免疫相关生物标志物。
