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Int J Toxicol. 2018 Mar/Apr;37(2):155-163. doi: 10.1177/1091581818757036. Epub 2018 Mar 19.

Trichloroethylene Alters Th1/Th2/Th17/Treg Paradigm in Mice: A Novel Mechanism for Chemically Induced Autoimmunity.

Author information

1
1 Institute of Dermatology, Anhui Medical University, Hefei, Anhui, People's Republic of China.
2
2 Center for Scientific Research, Anhui Medical University, Hefei, Anhui, People's Republic of China.
3
3 Department of Occupational Health and Environment Health, School of Public Health, Anhui Medical University, Hefei, Anhui, People's Republic of China.
4
4 Department of Nutrition, Chaohu Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.
5
5 Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.

Abstract

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-γ, 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.

KEYWORDS:

IFN-γ; IL-10; IL-17A; IL-4; Th1/Th2/Th17/Treg paradigm; trichloroethylene

PMID:
29554824
DOI:
10.1177/1091581818757036

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