Aryl Hydrocarbon Receptor-Deficient Mice Generate Normal Immune Responses to Model Antigens and Are Resistant to TCDD-Induced Immune Suppression

2001 ◽  
Vol 171 (3) ◽  
pp. 157-164 ◽  
Author(s):  
Beth A. Vorderstrasse ◽  
Linda B. Steppan ◽  
Allen E. Silverstone ◽  
Nancy I. Kerkvliet
Keyword(s):  
Immune Responses ◽  
Aryl Hydrocarbon Receptor ◽  
Immune Suppression ◽  
Aryl Hydrocarbon ◽  
Deficient Mice

Aryl-hydrocarbon Receptor-Deficient Mice Are Resistant to 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Toxicity

1996 ◽  
Vol 140 (1) ◽  
pp. 173-179 ◽  
Author(s):  
Pedro M. Fernandez-Salguero ◽  
David M. Hilbert ◽  
Stuart Rudikoff ◽  
Jerrold M. Ward ◽  
Frank J. Gonzalez
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Aryl Hydrocarbon ◽  
Tetrachlorodibenzo P Dioxin ◽  
Deficient Mice

scholarly journals Acyloxyacyl hydrolase modulates depressive-like behaviors through aryl hydrocarbon receptor

2019 ◽  
Vol 317 (2) ◽  
pp. R289-R300 ◽  
Author(s):  
Lizath M. Aguiniga ◽  
Wenbin Yang ◽  
Ryan E. Yaggie ◽  
Anthony J. Schaeffer ◽  
David J. Klumpp ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Therapeutic Target ◽  
Binding Sites ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Aryl Hydrocarbon ◽  
Acyloxyacyl Hydrolase ◽  
Deficient Mice ◽  
Pituitary Adrenal Axis

Corticotropin-releasing factor (CRF) regulates stress responses, and aberrant CRF signals are associated with depressive disorders. Crf expression is responsive to arachidonic acid (AA), where CRF is released from the hypothalamic paraventricular nucleus (PVN) to initiate the hypothalamic-pituitary-adrenal axis, culminating in glucocorticoid stress hormone release. Despite this biological and clinical significance, Crf regulation is unclear. Here, we report that acyloxyacyl hydrolase, encoded by Aoah, is expressed in the PVN, and Aoah regulates Crf through the aryl hydrocarbon receptor (AhR). We previously showed that AOAH-deficient mice mimicked interstitial cystitis/bladder pain syndrome, a condition frequently associated with comorbid anxiety and depression. With the use of novelty-suppressed feeding and sucrose preference assays to quantify rodent correlates of anxiety/depression, AOAH-deficient mice exhibited depressive behaviors. AOAH-deficient mice also had increased CNS AA, increased Crf expression in the PVN, and elevated serum corticosterone, consistent with dysfunction of the hypothalamic-pituitary-adrenal axis. The human Crf promoter has putative binding sites for AhR and peroxisome proliferator-activated receptor (PPARγ). PPARγ did not affect AA-dependent Crf expression in vitro, and conditional Pparγ knockout did not alter the AOAH-deficient depressive phenotype, despite previous studies implicating PPARγ as a therapeutic target for depression. In contrast, Crf induction was mediated by AhR binding sites in vitro and increased by AhR overexpression. Furthermore, conditional Ahr knockout rescued the depressive phenotype of AOAH-deficient mice. Finally, an AhR antagonist rescued the AOAH-deficient depressive phenotype. Together, our results demonstrate that Aoah is a novel genetic regulator of Crf mediated through AhR, and AhR is a therapeutic target for depression.

Aryl hydrocarbon receptor-deficient mice are protected from high fat diet-induced changes in metabolic rhythms

2017 ◽  
Vol 34 (3) ◽  
pp. 318-336 ◽  
Author(s):  
Cassie Jaeger ◽  
Canxin Xu ◽  
Mingwei Sun ◽  
Stacey Krager ◽  
Shelley A. Tischkau
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
High Fat Diet ◽  
High Fat ◽  
Aryl Hydrocarbon ◽  
Induced Changes ◽  
Deficient Mice

scholarly journals The Group 3 Innate Lymphoid Cell Defect in Aryl Hydrocarbon Receptor Deficient Mice Is Associated with T Cell Hyperactivation during Intestinal Infection

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0128335 ◽  
Author(s):  
Sagie Wagage ◽  
Gretchen Harms Pritchard ◽  
Lucas Dawson ◽  
Elizabeth L. Buza ◽  
Gregory F. Sonnenberg ◽  
...  
Keyword(s):  
T Cell ◽  
Aryl Hydrocarbon Receptor ◽  
Lymphoid Cell ◽  
Intestinal Infection ◽  
Innate Lymphoid Cell ◽  
Aryl Hydrocarbon ◽  
Group 3 ◽  
Deficient Mice ◽  
Cell Defect

scholarly journals A42 MICROBIAL METABOLISM OF DIETARY TRYPTOPHAN ENHANCES ARYL HYDROCARBON RECEPTOR ACTIVATION: IMPLICATIONS FOR IBD

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 50-51
Author(s):  
L Rondeau ◽  
A V Clarizio ◽  
J Jury ◽  
D L Gibson ◽  
P Bercik ◽  
...  
Keyword(s):  
16S Rrna ◽  
Gut Microbiota ◽  
Aryl Hydrocarbon Receptor ◽  
Healthy Subjects ◽  
Tryptophan Metabolism ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Aryl Hydrocarbon ◽  
Deficient Mice ◽  
Activation Capacity

Abstract Background Intestinal immune homeostasis is maintained by the interplay between microbiota and the mucosal immune system. Changes in gut microbiota have been associated with chronic intestinal conditions, such as inflammatory bowel disease (IBD). The aryl hydrocarbon receptor (AhR) is a transcription factor that is activated by dietary and environmental stimuli to control immune responses in the gut and homeostatic mechanisms at mucosal surfaces. In IBD, AhR expression is downregulated. Major agonists of AhR in the gut include microbial tryptophan metabolites such as indole derivatives, which are decreased in IBD patients. The mechanisms involved in tryptophan metabolism by bacteria and their implications in AhR activation and thus IBD pathogenesis are not well understood. Aims To investigate whether tryptophan metabolism by intestinal bacteria participates in AhR activation and IBD pathogenesis. Methods Microbiota profiles (16S rRNA Illumina) and activation of AhR (luciferase reporter assay) were determined in fecal samples from IBD patients (n=10) and healthy volunteers (n=10). Germ-free C57BL/6 mice were colonized with fecal slurries of 2 healthy subjects and 4 IBD patients (n=4 mice/donor) by oral gavage (humanized-mice). All mice were fed irradiated tryptophan diets with 0.1% or 1% tryptophan content for 14 days. Simultaneously, SPF Mucin 2 (Muc2) deficient mice (C57BL/6 background), which develop colitis spontaneously, were fed tryptophan diets (0.1%, 0.3% and 1% content). Activation of AhR was measured in feces using an AhR luciferase reporter assay. Inflammation was determined by immunohistochemistry and the characterization of immune infiltrate in colon cross-sections. Bacteria from human and mouse fecal samples were isolated and screened for their ability to produce indoles using biochemical reagents. Positive bacteria were identified by colony PCR and 16S rRNA Sanger sequencing. Results IBD patients had an altered fecal microbiota with a lower capacity to activate AhR compared to healthy subjects. Colonization of mice with microbiota from healthy subjects induced greater activation of AhR compared to mice colonized with microbiota from patients with IBD. Furthermore, increasing dietary tryptophan composition rescued the capacity to activate AhR. In Muc2 deficient mice, dietary tryptophan treatment enhanced AhR activation capacity and reduced infiltration of innate immune cells before the onset of colitis. Several AhR agonist producing bacterial species were identified and will be used in future experiments. Conclusions Activation of AhR is dependent on the gut microbiota and disease status of the donor. Dietary intervention with tryptophan enhances AhR activation capacity and may be a potential therapeutic avenue in IBD individuals with intestinal dysbiosis. Funding Agencies Farncombe Family Digestive Health Research Institute, Biocodex Microbiota Foundation

Aryl hydrocarbon receptor protects against viridans streptococci infection by activation of immune system through IL-17RA signaling

2015 ◽  
Vol 3 (2) ◽  
pp. 400-410
Author(s):  
Guowei Liang ◽  
Keyword(s):  
Immune Responses ◽  
Aryl Hydrocarbon Receptor ◽  
Bacterial Infections ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Microbial Infection ◽  
Viridans Streptococci ◽  
Coagulase Negative Staphylococci ◽  
Aryl Hydrocarbon

The majority of bacterial infections during neutropenia following high-dose chemotherapy or stem cell transplantation are caused by coagulase-negative staphylococci, a large number are due to viridans streptococci. Despite considerable progress in the understanding of the AhR-mediated regulation of immune responses, the role of AhR in bacterial infections has not been clearly demonstrated. In the study presented here, we sought to determine whether the aryl hydrocarbon receptor (AhR) would protect mice from infection with viridans streptococci. AhR enhances the inflammatory response to viridans streptococci stimuli. Specifically, neutrophil numbers and levels of inflammatory cytokines are often increased in mice treated with viridans streptococci. Furthermore, AhR activation through the IL-17RA is required for protection against viridans streptococcal infection. Taken together, we concluded that AhR plays an important role in optimal innate immunoprotection against microbial infection through the down-regulation of immune response.

Tissue distribution and function of the Aryl hydrocarbon receptor repressor (AhRR) in C57BL/6 and Aryl hydrocarbon receptor deficient mice

2005 ◽  
Vol 80 (4) ◽  
pp. 206-211 ◽  
Author(s):  
Thorsten Bernshausen ◽  
Bettina Jux ◽  
Charlotte Esser ◽  
Josef Abel ◽  
Ellen Fritsche
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Tissue Distribution ◽  
Aryl Hydrocarbon ◽  
And Function ◽  
Deficient Mice
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