Consequences of Aryl Hydrocarbon Receptor Activation in Crohn's Disease
type: CreativeWork
description: Activation of the aryl hydrocarbon (AhR), a ligand-activated transcription factor present in many immune cells, can trigger immunosuppressive responses through the generation of regulatory cells. Several AhR ligands exist in the diet including environmental contaminants, such as its prototypical ligand 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD), and natural sources, such as indole-3-carbinol (I3C) and indirubin. Crohn's disease, a chronic inflammatory state of the gastrointestinal tract, affects millions worldwide; however, the exact cause is unknown and treatments do not cure the disease. The role of the AhR in mucosal immune responses is not well understood to date so we aimed to understand the consequences of AhR activation in gut inflammatory responses. The overall hypothesis of this project is that AhR agonists found in the diet have the potential to dampen inflammation associated with Crohn's disease. The first goal of this project was to examine the role of AhR activation in the development and progression of colitis using TCDD and the natural ligand I3C. TCDD suppressed TNBS-induced colitis, as demonstrated by the decreased disease severity and dampened inflammation in the gut. TCDD-treated mice exhibited decreased inflammatory mediator production and increased frequency of regulatory cells, both Foxp3+ Tregs and dendritic cells (DCs) in gut immune tissues. In comparison, I3C suppressed disease severity in females but not males. Sex-specific effects on colonic cytokine production and gene expression were observed. The second goal of this project was to define the cellular mechanisms by which AhR ligands elicit their effects on important immune cell populations present in the gut. Therefore, we investigated the immunomodulatory effects of the dietary AhR ligands I3C and indirubin in bone marrow derived DCs (BMDCs). I3C-and indirubin-treated BMDCs upregulated the expression of immunoregulatory genes, such as ALDH1A, IDO, and TGFâ, and also drove the generation …
abstract: Activation of the aryl hydrocarbon (AhR), a ligand-activated transcription factor present in many immune cells, can trigger immunosuppressive responses through the generation of regulatory cells. Several AhR ligands exist in the diet including environmental contaminants, such as its prototypical ligand 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD), and natural sources, such as indole-3-carbinol (I3C) and indirubin. Crohn's disease, a chronic inflammatory state of the gastrointestinal tract, affects millions worldwide; however, the exact cause is unknown and treatments do not cure the disease. The role of the AhR in mucosal immune responses is not well understood to date so we aimed to understand the consequences of AhR activation in gut inflammatory responses. The overall hypothesis of this project is that AhR agonists found in the diet have the potential to dampen inflammation associated with Crohn's disease. The first goal of this project was to examine the role of AhR activation in the development and progression of colitis using TCDD and the natural ligand I3C. TCDD suppressed TNBS-induced colitis, as demonstrated by the decreased disease severity and dampened inflammation in the gut. TCDD-treated mice exhibited decreased inflammatory mediator production and increased frequency of regulatory cells, both Foxp3+ Tregs and dendritic cells (DCs) in gut immune tissues. In comparison, I3C suppressed disease severity in females but not males. Sex-specific effects on colonic cytokine production and gene expression were observed. The second goal of this project was to define the cellular mechanisms by which AhR ligands elicit their effects on important immune cell populations present in the gut. Therefore, we investigated the immunomodulatory effects of the dietary AhR ligands I3C and indirubin in bone marrow derived DCs (BMDCs). I3C-and indirubin-treated BMDCs upregulated the expression of immunoregulatory genes, such as ALDH1A, IDO, and TGFâ, and also drove the generation …
author: Benson, Jenna Marie
keywords: Aryl Hydrocarbon Receptor, Crohn', s Disease, Indirubin, Indole-3-Carbinol, Inflammation
date published: 2012-01-01T08:00:00Z
date modified: 2026-07-24T03:10:36Z
provider: University of Montana
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Montana