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Updated: Jun 8, 2026
Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
Role of the xenobiotic receptor in inflammatory bowel disease
Razvan Arsenescu1, Violeta Arsenescu, Jian Zhong
1Division of Digestive Diseases and Nutrition, University of Kentucky, Lexington, Kentucky 40536, USA.
Background:
Gene-environment interplay modulates inflammatory bowel diseases (IBD). Dioxin-like compounds can activate the aryl hydrocarbon receptor (AhR) and alter macrophage function as well as T-cell polarization. We hypothesized that attenuation of the AhR signaling pathway will ameliorate colitis in a murine model of IBD.
Methods:
Dextran sulfate sodium (DSS) colitis was induced in C57BL/6 AhR null mice (AhR(-/-) ), heterozygous mice (AhR(-/+) ), and their wildtype (WT) littermates. Clinical and morphopathological parameters were used to compare the groups.
Patients:
AhR pathway activation was analyzed in biopsy specimens from 25 IBD patients and 15 healthy controls.
Results:
AhR(-/-) mice died before the end of the treatment. However, AhR(-/+) mice exhibited decreased disease activity compared to WT mice. The AhR(-/+) mice expressed less proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) (6.1- versus 15.7-fold increase) and IL17 (23.7- versus 67.9-fold increase) and increased antiinflammatory IL-10 (2.3-fold increase) compared with the AhR(+/+) mice in the colon. Colonic macrophage infiltration was attenuated in the AhR(-/+) group. AhR and its downstream targets were significantly upregulated in IBD patients versus control (CYP1A1 -19.9, and IL8- 10-fold increase).
Conclusions:
Attenuation of the AhR receptor expression resulted in a protective effect during DSS-induced colitis, while the absence of AhR exacerbated the disease. Abnormal AhR pathway activation in the intestinal mucosa of IBD patients may promote chronic inflammation. Modulation of AhR signaling pathway via the diet, cessation of smoking, or administration of AhR antagonists could be viable strategies for the treatment of IBD.
Insights
Attenuation of the aryl hydrocarbon receptor (AhR) signaling pathway ameliorates colitis in mice. This suggests AhR pathway modulation may offer new therapeutic strategies for inflammatory bowel diseases (IBD).
Area of Science:
- Immunology
- Gastroenterology
- Pharmacology
Background:
- Gene-environment interactions significantly influence inflammatory bowel diseases (IBD).
- The aryl hydrocarbon receptor (AhR) signaling pathway is implicated in immune regulation, including macrophage function and T-cell polarization.
- Dioxin-like compounds are known activators of the AhR pathway.
Purpose of the Study:
- To investigate the role of the AhR signaling pathway in dextran sulfate sodium (DSS)-induced colitis, a model of IBD.
- To determine if attenuating AhR signaling can ameliorate colitis.
- To analyze AhR pathway activation in IBD patients.
Main Methods:
- Induction of DSS colitis in AhR null (AhR(-/-)), heterozygous (AhR(-/+)), and wildtype (WT) mice.
- Assessment of clinical and morphopathological parameters to compare disease severity.
- Analysis of AhR pathway activation in colonic biopsy specimens from IBD patients and healthy controls.
Main Results:
- AhR(-/-) mice exhibited lethality, while AhR(-/+) mice showed reduced disease activity compared to WT mice.
- AhR(-/+) mice displayed lower levels of pro-inflammatory cytokines (TNF-α, IL17) and higher levels of anti-inflammatory IL-10 in the colon.
- Reduced colonic macrophage infiltration was observed in AhR(-/+) mice. AhR and its targets were upregulated in IBD patients.
Conclusions:
- Attenuation of AhR expression confers protection in DSS-induced colitis, whereas AhR absence exacerbates the disease.
- Aberrant AhR pathway activation in the intestinal mucosa of IBD patients may contribute to chronic inflammation.
- Modulating the AhR signaling pathway through diet, smoking cessation, or AhR antagonists presents potential therapeutic avenues for IBD treatment.
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