TCDD: An Environmental Immunotoxicant Reveals a Novel Pathway of Immunoregulation—A 30-Year Odyssey

@article{Kerkvliet2012TCDDAE,
  title={TCDD: An Environmental Immunotoxicant Reveals a Novel Pathway of Immunoregulation—A 30-Year Odyssey},
  author={Nancy I Kerkvliet},
  journal={Toxicologic Pathology},
  year={2012},
  volume={40},
  pages={138 - 142}
}
  • N. Kerkvliet
  • Published 1 February 2012
  • Biology
  • Toxicologic Pathology
I was honored to be the keynote speaker at the 30th Annual Society of Toxicologic Pathology Symposium “Toxicologic Pathology and the Immune System.” I had the opportunity to reminisce about events in the 1970s that set the stage for the birth and subsequent growth of the field of immunotoxicology and to summarize my research career that has spanned the past 40 years as well. An initial focus on the immunotoxicity of pentachlorophenol led my laboratory into the aryl hydrocarbon receptor (AHR… 
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29 Citations
Background Citations
10
Methods Citations
1
Results Citations
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29 Citations

Citation Type

Citation Type

Immunotoxicity of Xenobiotics in Fish: A Role for the Aryl Hydrocarbon Receptor (AhR)?
TLDR
The aims of the present review are to critically discuss the available knowledge on the expression and possible function of the aryl hydrocarbon receptor (AhR) and the impact of AhR-activating xenobiotics on the immune systems of fish at the levels of immune gene expression, immune cell proliferation and immune cell function, immune pathology, and resistance to infectious disease.
The immunotoxic effects of dual exposure to PCP and TCDD.
Aryl Hydrocarbon Receptor and Kynurenine: Recent Advances in Autoimmune Disease Research
TLDR
The potential link between AHR and IDO/tryptophan metabolites, and the involvement of several novel related factors (such as microRNA) in the development of autoimmune diseases are discussed.
A historical perspective of immunotoxicology
  • M. Luster
  • Biology
    Journal of immunotoxicology
  • 2014
Abstract An historical perspective of immunotoxicology is presented beginning from early observations in which exposure to workplace environments led to unexpected immune-mediated lung diseases to…
P69: Dioxin-mediated regulation of expression IL-12 family cytokines in human macrophages as a factor of tumor promotion by TCDD
2,3,7,8-Tetrachloodibenzo-p-dioxin affects the differentiation of CD4 helper T cell.
Environmental immune disruptors, inflammation and cancer risk.
TLDR
The role that the innate immune cells of inflammatory responses play in tumorigenesis is reviewed and the evidence linking environmental toxicant exposures with perturbation in the balance between pro- and anti-inflammatory responses is reviewed.
The roles of aryl hydrocarbon receptor in immune responses.
TLDR
The roles of Ahr in macrophages and T cells are discussed and studies examining Ahr activation in other cell types have revealed additional contributions to B cell and osteoblast/osteoclast differentiation.
Expression dynamics of the REL, RELA, and IRF1 transcription factors in U937 macrophages after dioxin exposure
TLDR
Quantitative real-time PCR demonstrates that the expression of the DREs residing in the IRF1, REL, and RELA regulatory regions via the AhR signaling pathway increases in a statistically significant manner 1 h after exposure to 10 nM TCDD.
Benzimidazoisoquinolines: A New Class of Rapidly Metabolized Aryl Hydrocarbon Receptor (AhR) Ligands that Induce AhR-Dependent Tregs and Prevent Murine Graft-Versus-Host Disease
TLDR
A screen for novel Treg-inducing compounds based on understanding of the mechanisms of Treg induction by the well-characterized immunosuppressive AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is designed, providing strong support for development of select BBQs that activate the AhR to induce Tregs for treatment of immune-mediated diseases.
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References

SHOWING 1-10 OF 40 REFERENCES
Suppression of experimental autoimmune uveoretinitis by inducing differentiation of regulatory T cells via activation of aryl hydrocarbon receptor.
TLDR
Activation of AHR by TCDD markedly suppressed autoimmune uveoretinitis through mechanisms that expand CD25(+)Foxp3(+) T(reg) cells and interfere with the activation of Th1 and Th17 cells.
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) renders influenza virus-specific CD8+ T cells hyporesponsive to antigen.
  • K. Mitchell, B. Lawrence
  • Biology, Medicine
    Toxicological sciences : an official journal of the Society of Toxicology
  • 2003
TLDR
The observation that neither proliferation nor IFNgamma production by CD8+ T cells could be completely restored, even when cells were provided with optimal stimulation, suggests that exposure to TCDD drives antigen-specific CD8- T cells into a state of unresponsiveness similar to anergy.
Aryl hydrocarbon receptor-deficient mice generate normal immune responses to model antigens and are resistant to TCDD-induced immune suppression.
TLDR
Results from these studies showed that AhR-deficient mice were able to mount normal productive immune responses to both model antigens and that neither the cellular nor the humoral response was suppressed by exposure to TCDD, and confirmed the findings of previous studies that have indicated the AhR plays an obligatory role in T CDD-induced immune suppression.
Humoral immunotoxicity of polychlorinated diphenyl ethers, phenoxyphenols, dioxins and furans present as contaminants of technical grade pentachlorophenol.
The effects of TCDD on the activation of ovalbumin (OVA)-specific DO11.10 transgenic CD4(+) T cells in adoptively transferred mice.
TLDR
Data suggest that TCDD may interfere with the survival and/or differentiation of OVA-specific T-helper cells, and demonstrate for the first time the potential of the DO11.10 adoptive transfer system to directly assess immunotoxic effects of xenobiotics on antigen-specific CD4(+) T cells in vivo.
Cutting Edge: Activation of the Aryl Hydrocarbon Receptor by 2,3,7,8-Tetrachlorodibenzo-p-dioxin Generates a Population of CD4+CD25+ Cells with Characteristics of Regulatory T Cells1
TLDR
A novel role for AhR is suggested in the induction of regulatory T cells in vitro and a new perspective on the mechanisms that underlie the profound immune suppression induced by exposure to TCDD is provided.
Role of the Ah locus in suppression of cytotoxic T lymphocyte activity by halogenated aromatic hydrocarbons (PCBs and TCDD): structure-activity relationships and effects in C57Bl/6 mice congenic at the Ah locus.
A Role of the Aryl Hydrocarbon Receptor in Attenuation of Colitis
TLDR
The findings about the potential role of AhR activators in epithelial immune regulation aid the understanding of mucosal homeostasis and inflammatory bowl disease (IBD) and suggest that AhR activation has therapeutic value for the treatment of IBD.
Immunotoxicity of technical pentachlorophenol (PCP-T): depressed humoral immune responses to T-dependent and T-independent antigen stimulation in PCP-T exposed mice.
T lymphocytes are direct, aryl hydrocarbon receptor (AhR)-dependent targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): AhR expression in both CD4+ and CD8+ T cells is necessary for full suppression of a cytotoxic T lymphocyte response by TCDD.
TLDR
Results indicate that direct AhR-dependent effects of TCDD occur in both CD4+ and CD8+ T cell subsets and both Tcell subsets contribute to the full suppression of the CTL response by T CDD.
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