Developmental trichloroethylene exposure enhances predictive markers of autoimmunity in a sex-specific manner in disease-resistant female mice

Abstract

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.