Ah Receptor in Different Tissues of C57BL/6J and DBA/2J Mice: Use of Competitive Polymerase Chain Reaction to Measure Ah-Receptor mRNA Expression

Li, W.; Donat, Susanne; Döhr, Olaf; Unfried, Klaus; Abel, Josef

doi:10.1006/abbi.1994.1501

Cited by 71 publications

(35 citation statements)

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“…ARNT is abundantly expressed in immune tissue including the thymus (51)(52)(53)(54). However, the present results reveal no role for ARNT in the development of functional thymus or T cells.…”

Section: Discussionmentioning

confidence: 99%

T Cell-Specific Disruption of Arylhydrocarbon Receptor Nuclear Translocator (Arnt) Gene Causes Resistance to 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Thymic Involution

Tomita

Jiang

Ueno

et al. 2003

The Journal of Immunology

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The arylhydrocarbon receptor nuclear translocator (ARNT) is a member of the basic helix-loop-helix, PER-ARNT-SIM family of heterodimeric transcription factors, and serves as a dimerization partner for arylhydrocarbon receptor (AHR) and hypoxia-inducible factor-1α. To assess the function of ARNT in T cells, we disrupted the Arnt gene specifically in T cells of mice by conditional gene targeting using T cell-specific p56lck-Cre (Lck-Cre) transgenic Arnt-floxed mice. Thus generated, T cell-specific Arnt-disrupted mice (Lck-Cre;Arntflox/Δ transgenic mice) exhibited complete loss of the expression of ARNT protein only in T cells, and were viable and appeared normal. The Arnt-disrupted T cells in the thymus were phenotypically and histologically normal. The Arnt-deficient T cells in the spleen were capable of responding to TCR stimulation in vitro. However, unlike normal mice in which exposure to the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an AHR ligand, resulted in thymic involution, the thymus of Lck-Cre;Arntflox/Δ mice were resistant to TCDD treatment in vivo. In contrast, benzo(a)pyrene, another AHR ligand, still caused thymic involution in Lck-Cre;Arntflox/Δ mice. Finally, fetal thymus organ culture using Lck-Cre;Arntflox/Δ and K5-Cre;Arntflox/Δ (epithelial cell-specific Arnt-disrupted mice) showed that thymocytes rather than thymic epithelial cells are predominantly responsible for TCDD-induced thymic atrophy. Our results indicate that ARNT in T lineage cells is essential for TCDD-mediated thymic involution.

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Section: Discussionmentioning

confidence: 99%

T Cell-Specific Disruption of Arylhydrocarbon Receptor Nuclear Translocator (Arnt) Gene Causes Resistance to 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Thymic Involution

Tomita

Jiang

Ueno

et al. 2003

The Journal of Immunology

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“…at ASPET Journals on May 11, 2018May 11, dmd.aspetjournals.org 1994May 11, , 1998Li et al, 1994;Moi et al, 1994;Choi et al, 1997;McMahon et al, 2001;Bookout et al, 2006). The present study is the first to quantitatively compare expression of Nrf2 in various segments of the small intestine, the large intestine, and in several portions of the female reproductive tract.…”

Section: Xenobiotic Induction Of Car and Other Transcription Factorsmentioning

confidence: 96%

Importance of Hepatic Induction of Constitutive Androstane Receptor and Other Transcription Factors That Regulate Xenobiotic Metabolism and Transport

Petrick¹,

Klaassen²

2007

Drug Metab Dispos

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ABSTRACT:Aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor-␣ (PPAR␣), and nuclear factor-E2-related factor 2 (Nrf2) are transcription factors that mediate xenobiotic induction of biotransformation enzymes and transporters. The purpose of this study was to determine the tissue distribution and xenobiotic induction of these transcription factors and their associated target genes in mice. Many of these transcription factors were most highly expressed in extrahepatic tissues. CAR expression in female liver was twice that in male liver. This corresponded with greater induction of the CAR target genes Cyp2b10 and multidrug resistance-associated protein

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“…In the lung, CYP1A1 mRNA was detected in the wild-type mice. The lung is reported to express the highest level of AhR mRNA among the tissues examined, including the thymus and spleen, in the mice (38). Recently, endogenous ligand was isolated from porcine lung (39).…”

Section: Generation Of T Cell-specific Ca-ahr Tg Micementioning

confidence: 99%

Constitutively Active Aryl Hydrocarbon Receptor Expressed Specifically in T-Lineage Cells Causes Thymus Involution and Suppresses the Immunization-Induced Increase in Splenocytes

Nohara

Pan

Tsukumo

et al. 2005

The Journal of Immunology

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The aryl hydrocarbon receptor (AhR) is a transcription factor belonging to the basic helix-loop-helix-PER-ARNT-SIM superfamily. Xenobiotics, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, bind the receptor and trigger diverse biological reactions. Thymocyte development and T cell-dependent immune reactions are sensitive targets of AhR-dependent 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity. However, the exact role of the AhR in T cells in animals exposed to exogenous ligands has not been clarified because indirect effects of activated AhR in other cell types cannot be excluded. In this study, we generated transgenic (Tg) mice expressing a constitutively active mutant of AhR under the regulation of a T cell-specific CD2 promoter to examine AhR function in T cells. The mRNAs of the constitutively active mutant of AhR and an AhR-induced gene, CYP1A1, were expressed in the thymus and spleen of the Tg mice. The transgene expression was clearly detected in the thymocytes, CD4, and CD8 T cells, but not in the B cells or thymus stromal cells. These Tg mice had a decreased number of thymocytes and an increased percentage of CD8 single-positive thymocytes, but their splenocytes were much less affected. By contrast, the increase in number of T cells and B cells taking place in the spleen after immunization was significantly suppressed in the Tg mice. These results clearly show that AhR activation in the T-lineage cells is directly involved in thymocyte loss and skewed differentiation. They also indicate that AhR activation in T cells and not in B cells suppresses the immunization-induced increase in both T cells and B cells.

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Ah Receptor in Different Tissues of C57BL/6J and DBA/2J Mice: Use of Competitive Polymerase Chain Reaction to Measure Ah-Receptor mRNA Expression

Cited by 71 publications

References 0 publications

T Cell-Specific Disruption of Arylhydrocarbon Receptor Nuclear Translocator (Arnt) Gene Causes Resistance to 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Thymic Involution

T Cell-Specific Disruption of Arylhydrocarbon Receptor Nuclear Translocator (Arnt) Gene Causes Resistance to 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Thymic Involution

Importance of Hepatic Induction of Constitutive Androstane Receptor and Other Transcription Factors That Regulate Xenobiotic Metabolism and Transport

Constitutively Active Aryl Hydrocarbon Receptor Expressed Specifically in T-Lineage Cells Causes Thymus Involution and Suppresses the Immunization-Induced Increase in Splenocytes

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