%0 Journal Article
%T Trichloroethylene Alters Th1/Th2/Th17/Treg Paradigm in Mice: A Novel Mechanism for Chemically Induced Autoimmunity
%A Changhao Wu
%A Cheng Zhang
%A Hui Wang
%A Jia-xiang Zhang
%A Min Liu
%A Peng Yang
%A Qi-xing Zhu
%A Shu-long Li
%A Tong Shen
%A Yun Yu
%J International Journal of Toxicology
%@ 1092-874X
%D 2018
%R 10.1177/1091581818757036
%X The role of environmental factors in autoimmune diseases has been increasingly recognized. While major advance has been made in understanding biological pathogen-induced autoimmune diseases, chemically triggered autoimmunity is poorly understood. Trichloroethylene (TCE), a common environmental pollutant, has recently been shown to induce autoimmunity. This study explored whether TCE could cause imbalance of T helper (Th) cell subsets which would contribute to the pathogenesis of TCE-induced medicamentosa-like dermatitis. BALB/c mice were treated with TCE via drinking water at doses of 2.5 or 5.0 mg/mL for 2, 4, 8, 12, and 16 weeks. Trichloroethylene exposure caused time- and dose-dependent increase in Th1, Th2, and Th17 and decrease in regulatory cell (Treg) in the spleen at 2, 4, 8, 12, and 16 weeks, with greatest changes mainly at 4 weeks. These effects were mirrored by similar changes in the expression of their corresponding cytokines interferon-¦Ã, interleukin 4 (IL-4), IL-17A, and IL-10. Mechanistically, these phenotypic changes were accounted for by alterations to their respective master transcription factors T-box expressed in T cells, GATA-binding protein 3, Retinoic acid-related orphan receptor ct (RORct), and forkhead box P3. Of interest, TCE treatment shifted the ratios of Th1/Th2 and Th17/Treg; specifically, TCE increased Th17/Treg. These findings provide the first evidence that TCE exposure significantly changes the Th1/Th2/Th17/Treg paradigm and their specific cytokines driven by altered master transcription factors. This may promote autoimmune reactions in the pathogenesis of TCE-induced skin sensitization and associated damage to other tissues
%K trichloroethylene
%K Th1/Th2/Th17/Treg paradigm
%K IFN-¦Ã
%K IL-4
%K IL-17A
%K IL-10
%U https://journals.sagepub.com/doi/full/10.1177/1091581818757036