2,3,7,8-Tetrachloodibenzo-p-dioxin affects the differentiation of CD4 helper T cell

Chengfang Pang, Conghui Zhu, Yuanyuan Zhang, Ying Ge, Shujuan Li, Shouliang Huo, Tuan Xu, Roland H. Stauber, Bin Zhao*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the most toxic congener of dioxins, is a persistent and ubiquitous environmental contaminant. Although the immunotoxic effects of TCDD have been reported, the mechanisms underlying these effects are still unclear. In this study, we have determined the toxic effects of TCDD on thymocytes and splenic T cells with in vitro cell culture systems. Magnetically isolated mouse splenic Th cells, Treg cells and the mixed spleen lymphocytes (SLC) were cultured and treated with TCDD and the differentiation of CD4 Th cells was determined by flow cytometery. Our results showed that different concentrations of TCDD caused immunotoxic effects through different toxicological mechanisms in both the purified mouse splenic Th cells and the mixed SLC. The low dose exposure to TCDD triggered regulatory effects in the immune system, while the high dose TCDD exposure resulted in severe immune toxicity. Notably, a decline of Treg subset was observed, suggesting an imbalanced immune regulation by TCDD treatment, as well as a possible decrease of TCDD's indirect effects on bystander immune cells. Our CD4 Th subset co-culture experiments showed that TCDD-induced pathobiology depended on immune cell balance, suggesting that cytokine-induced micro-environments further modulated toxic effects associated with TCDD exposure.
Original languageEnglish
JournalToxicology Letters
Volume311
Pages (from-to)49-57
Number of pages9
ISSN0378-4274
DOIs
Publication statusPublished - 2019

Keywords

  • Dioxin
  • TCDD
  • Helper T cell
  • Cell differentiation
  • Immune suppression
  • AhR

Cite this

Pang, Chengfang ; Zhu, Conghui ; Zhang, Yuanyuan ; Ge, Ying ; Li, Shujuan ; Huo, Shouliang ; Xu, Tuan ; Stauber, Roland H. ; Zhao, Bin. / 2,3,7,8-Tetrachloodibenzo-p-dioxin affects the differentiation of CD4 helper T cell. In: Toxicology Letters. 2019 ; Vol. 311. pp. 49-57.
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title = "2,3,7,8-Tetrachloodibenzo-p-dioxin affects the differentiation of CD4 helper T cell",
abstract = "2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the most toxic congener of dioxins, is a persistent and ubiquitous environmental contaminant. Although the immunotoxic effects of TCDD have been reported, the mechanisms underlying these effects are still unclear. In this study, we have determined the toxic effects of TCDD on thymocytes and splenic T cells with in vitro cell culture systems. Magnetically isolated mouse splenic Th cells, Treg cells and the mixed spleen lymphocytes (SLC) were cultured and treated with TCDD and the differentiation of CD4 Th cells was determined by flow cytometery. Our results showed that different concentrations of TCDD caused immunotoxic effects through different toxicological mechanisms in both the purified mouse splenic Th cells and the mixed SLC. The low dose exposure to TCDD triggered regulatory effects in the immune system, while the high dose TCDD exposure resulted in severe immune toxicity. Notably, a decline of Treg subset was observed, suggesting an imbalanced immune regulation by TCDD treatment, as well as a possible decrease of TCDD's indirect effects on bystander immune cells. Our CD4 Th subset co-culture experiments showed that TCDD-induced pathobiology depended on immune cell balance, suggesting that cytokine-induced micro-environments further modulated toxic effects associated with TCDD exposure.",
keywords = "Dioxin, TCDD, Helper T cell, Cell differentiation, Immune suppression, AhR",
author = "Chengfang Pang and Conghui Zhu and Yuanyuan Zhang and Ying Ge and Shujuan Li and Shouliang Huo and Tuan Xu and Stauber, {Roland H.} and Bin Zhao",
year = "2019",
doi = "10.1016/j.toxlet.2019.04.015",
language = "English",
volume = "311",
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journal = "Toxicology Letters",
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Pang, C, Zhu, C, Zhang, Y, Ge, Y, Li, S, Huo, S, Xu, T, Stauber, RH & Zhao, B 2019, '2,3,7,8-Tetrachloodibenzo-p-dioxin affects the differentiation of CD4 helper T cell', Toxicology Letters, vol. 311, pp. 49-57. https://doi.org/10.1016/j.toxlet.2019.04.015

2,3,7,8-Tetrachloodibenzo-p-dioxin affects the differentiation of CD4 helper T cell. / Pang, Chengfang; Zhu, Conghui; Zhang, Yuanyuan; Ge, Ying; Li, Shujuan; Huo, Shouliang; Xu, Tuan; Stauber, Roland H.; Zhao, Bin.

In: Toxicology Letters, Vol. 311, 2019, p. 49-57.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - 2,3,7,8-Tetrachloodibenzo-p-dioxin affects the differentiation of CD4 helper T cell

AU - Pang, Chengfang

AU - Zhu, Conghui

AU - Zhang, Yuanyuan

AU - Ge, Ying

AU - Li, Shujuan

AU - Huo, Shouliang

AU - Xu, Tuan

AU - Stauber, Roland H.

AU - Zhao, Bin

PY - 2019

Y1 - 2019

N2 - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the most toxic congener of dioxins, is a persistent and ubiquitous environmental contaminant. Although the immunotoxic effects of TCDD have been reported, the mechanisms underlying these effects are still unclear. In this study, we have determined the toxic effects of TCDD on thymocytes and splenic T cells with in vitro cell culture systems. Magnetically isolated mouse splenic Th cells, Treg cells and the mixed spleen lymphocytes (SLC) were cultured and treated with TCDD and the differentiation of CD4 Th cells was determined by flow cytometery. Our results showed that different concentrations of TCDD caused immunotoxic effects through different toxicological mechanisms in both the purified mouse splenic Th cells and the mixed SLC. The low dose exposure to TCDD triggered regulatory effects in the immune system, while the high dose TCDD exposure resulted in severe immune toxicity. Notably, a decline of Treg subset was observed, suggesting an imbalanced immune regulation by TCDD treatment, as well as a possible decrease of TCDD's indirect effects on bystander immune cells. Our CD4 Th subset co-culture experiments showed that TCDD-induced pathobiology depended on immune cell balance, suggesting that cytokine-induced micro-environments further modulated toxic effects associated with TCDD exposure.

AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the most toxic congener of dioxins, is a persistent and ubiquitous environmental contaminant. Although the immunotoxic effects of TCDD have been reported, the mechanisms underlying these effects are still unclear. In this study, we have determined the toxic effects of TCDD on thymocytes and splenic T cells with in vitro cell culture systems. Magnetically isolated mouse splenic Th cells, Treg cells and the mixed spleen lymphocytes (SLC) were cultured and treated with TCDD and the differentiation of CD4 Th cells was determined by flow cytometery. Our results showed that different concentrations of TCDD caused immunotoxic effects through different toxicological mechanisms in both the purified mouse splenic Th cells and the mixed SLC. The low dose exposure to TCDD triggered regulatory effects in the immune system, while the high dose TCDD exposure resulted in severe immune toxicity. Notably, a decline of Treg subset was observed, suggesting an imbalanced immune regulation by TCDD treatment, as well as a possible decrease of TCDD's indirect effects on bystander immune cells. Our CD4 Th subset co-culture experiments showed that TCDD-induced pathobiology depended on immune cell balance, suggesting that cytokine-induced micro-environments further modulated toxic effects associated with TCDD exposure.

KW - Dioxin

KW - TCDD

KW - Helper T cell

KW - Cell differentiation

KW - Immune suppression

KW - AhR

U2 - 10.1016/j.toxlet.2019.04.015

DO - 10.1016/j.toxlet.2019.04.015

M3 - Journal article

C2 - 31014974

VL - 311

SP - 49

EP - 57

JO - Toxicology Letters

JF - Toxicology Letters

SN - 0378-4274

ER -