A constitutively active aryl hydrocarbon receptor causes loss of peritoneal B1 cells

doi:10.1016/S0006-291X(03)00185-2

Biochemical and Biophysical Research Communications

Volume 302, Issue 2, 7 March 2003, Pages 336-341

https://doi.org/10.1016/S0006-291X(03)00185-2 Get rights and content

Abstract

The dioxin/aryl hydrocarbon (Ah) receptor functions as a ligand-activated transcription factor that mediates toxicity of dioxins and related environmental pollutants. We have developed a transgenic mouse model that expresses a constitutively active Ah receptor. The immune system is one of the most sensitive target organs for dioxin toxicity and we have therefore investigated alterations of different lymphocyte populations in these mice. The population of mature bone-marrow derived B cells was enlarged, consistent with previous findings in dioxin exposed mice. In contrast, the peritoneal population of CD5-expressing B cells (B1 cells) was significantly diminished. This is the first study that demonstrates the effect of an activated Ah receptor on B1 cells. Since these cells are important mediators of innate immunity against pathogens such as Influenza virus, these results may explain the decreased resistance against infections that has been documented after dioxin exposure.

Section snippets

Materials and methods

Animals and RNA isolation. CA-AhR mice [17] bred to homozygosity and wild-type control animals were of the same mixed genetic background and were matched in each experiment according to age and sex. The animals were kept in ventilated filter top cages, exposed to a 12 h light/dark cycle, and received water and standard rodent feed (RM3, Special Diet Services, Essex, UK) ad libitum. Animals were sacrificed by CO₂ asphyxiation followed by cervical dislocation or cervical dislocation only. Tissues

Expression of the CA-AhR and the target gene CYP1A1 in lymphatic tissues

Expression of the CA-AhR in the transgenic mice is regulated by the SV40 virus SRα promoter and the Eμ enhancer from the immunoglobulin heavy chain locus [21]. As previously described [17], CA-AhR is expressed in thymus and spleen but also in axillar, inguinal, and mesenterial lymph nodes (Fig. 1A). In contrast to organs from wild-type mice the Ah receptor target gene CYP1A1 was expressed in all lymphatic organs analyzed from the CA-AhR animals, demonstrating constitutive transcriptional

Acknowledgements

This work was supported by the Swedish Cancer Society, The Foundation for Strategic Environmental Research, The Swedish Council for Working Life, and The Swedish Council for Environment Agricultural Sciences and Spatial Planning. We thank Gunilla Scheu for the technical support.

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The AhR signalling might regulate the development and/or homeostasis of B-1 cells. In mice expressing a constitutively active AhR (CA-AhR), CD5+IgMhighB220low B-1 cells in peritoneal cavity are significantly reduced [49]. However, the detailed analysis and the mechanism causing this abnormality remain elusive.
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^☆: Abbreviations: Ah, aryl hydrocarbon; CA-AhR, constitutively active Ah receptor; Arnt, Ah receptor nuclear translocator; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; CYP1A1, cytochrome P450 1A1; GAPDH, glyceraldehyde-3-phosphate dehydrogenase.

¹: Present address: Department of Bioscience, AstraZeneca R&D Södertälje, S-151 85 Södertälje, Sweden.

²: Present address: NeuroNova AB, Fiskartorpsvägen 15A, S-114 33 Stockholm, Sweden.

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A constitutively active aryl hydrocarbon receptor causes loss of peritoneal B1 cells☆

Abstract

Section snippets

Materials and methods

Expression of the CA-AhR and the target gene CYP1A1 in lymphatic tissues

Acknowledgements

Toxicol. Lett.

Biochem. Pharmacol.

Toxicology

Fundam. Appl. Toxicol.

Toxicol. Appl. Pharmacol.

Arch. Biochem. Biophys.

Toxicol. Appl. Pharmacol.

Arch. Biochem. Biophys.

J. Biol. Chem.

Immunity

Biochem. Biophys. Res. Commun.

Immunity

Short-term toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in laboratory animals: effects, mechanisms, and animal models

Pharmacol. Rev.

Induction of cytochrome P4501A1

Annu. Rev. Pharmacol. Toxicol.

Immunological effects of chlorinated dibenzo-p-dioxins

Environ. Health Perspect.

2,3,7,8-Tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity

Annu. Rev. Pharmacol. Toxicol.

Immunologic effects of background exposure to polychlorinated biphenyls and dioxins in dutch preschool children

Environ. Health Perspect.