Trichloroethylene Alters Th1/Th2/Th17/Treg Paradigm in Mice: A Novel Mechanism for Chemically Induced Autoimmunity
| Autor: | Shu-Long Li, Yun Yu, Changhao Wu, Hui Wang, Qi-Xing Zhu, Cheng Zhang, Tong Shen, Peng Yang, Min Liu, Jiaxiang Zhang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell Autoimmunity Spleen Biology Toxicology medicine.disease_cause T-Lymphocytes Regulatory Pathogenesis 03 medical and health sciences medicine Animals Transcription factor Interleukin 4 Orphan receptor Mice Inbred BALB C T-Lymphocytes Helper-Inducer Trichloroethylene Interleukin 10 030104 developmental biology medicine.anatomical_structure Immunology Solvents Cytokines Female |
| Zdroj: | International Journal of Toxicology. 37:155-163 |
| ISSN: | 1092-874X 1091-5818 |
| DOI: | 10.1177/1091581818757036 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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