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Published on: April 21, 2015
Aryl hydrocarbon receptor activation modulates CD8αα+TCRαβ+ IELs and suppression of colitis manifestations in mice
Weigang Chen1, Aimin Pu1, Baifa Sheng1
1Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Background:
This research is dedicated to investigating the effects and potential mechanism of action of the aryl hydrocarbon receptor on the intestinal mucosal immune system in dextran sulfate sodium (DSS)-induced colitis.
Methods:
Colitis was induced by the administration of 3% DSS to wild-type C57BL/6J mice for 7days. 6-formylindolo(3, 2-b)carbazole (FICZ), an endogenous agonist of the aryl hydrocarbon receptor (AhR), was given intraperitoneally on a daily basis beginning 2days after the start of DSS administration. The mice were weighed and assessed, and colon tissues were measured. Intraepithelial lymphocytes (IELs) were isolated from the colon and examined by flow cytometry and quantitative real-time PCR.
Results:
FICZ ameliorated DSS-induced colitis, resulting in a reduced disease activity index and improvement in the histology and length of the colon. Colitis reduced the percentage and number of CD8αα+TCRαβ+ IELs. FICZ prevented the reduction in the numbers of CD8αα+TCRαβ+ IELs by upregulating the expression of the IL-15 receptor and the aryl hydrocarbon receptor (AhR), and attenuating the apoptotic rate of CD8αα+TCRαβ+ IELs. Finally, IL-10 was increased and IFN-γ was decreased in CD8αα+TCRαβ+ IELs by FICZ administration in DSS-induced colitis.
Conclusions:
The results suggest that AhR activation ameliorated DSS-induced acute colitis, in a manner that is associated with the local expansion and functions of CD8αα+TCRαβ+ IELs in acute colitis. The findings indicate that AhR-related ligands might be targeted as novel drug targets for IBD.
Insights
Aryl hydrocarbon receptor (AhR) activation ameliorated dextran sulfate sodium (DSS)-induced colitis in mice. This involved protecting intestinal CD8αα+TCRαβ+ intraepithelial lymphocytes, suggesting AhR ligands as potential treatments for inflammatory bowel disease (IBD).
Area of Science:
- Immunology
- Gastroenterology
- Pharmacology
Background:
- Investigating the role of the aryl hydrocarbon receptor (AhR) in the intestinal immune system during dextran sulfate sodium (DSS)-induced colitis.
- Understanding the molecular mechanisms underlying AhR's influence on mucosal immunity in colitis models.
Purpose of the Study:
- To determine the therapeutic potential of AhR activation in DSS-induced colitis.
- To elucidate the impact of AhR signaling on intestinal immune cells, specifically CD8αα+TCRαβ+ intraepithelial lymphocytes (IELs).
Main Methods:
- Induction of colitis in C57BL/6J mice using 3% DSS.
- Administration of 6-formylindolo(3, 2-b)carbazole (FICZ), an AhR agonist, to DSS-treated mice.
- Isolation and analysis of colonic intraepithelial lymphocytes (IELs) via flow cytometry and quantitative real-time PCR.
Main Results:
- FICZ treatment significantly ameliorated DSS-induced colitis, improving disease activity index, colon histology, and length.
- FICZ administration prevented the reduction of CD8αα+TCRαβ+ IELs by upregulating IL-15 receptor and AhR expression, while reducing their apoptotic rate.
- FICZ modulated cytokine production in CD8αα+TCRαβ+ IELs, increasing IL-10 and decreasing IFN-γ levels.
Conclusions:
- AhR activation demonstrates a therapeutic effect on acute DSS-induced colitis, linked to the expansion and function of CD8αα+TCRαβ+ IELs.
- The findings highlight AhR as a potential therapeutic target for inflammatory bowel disease (IBD).
- Targeting AhR-related ligands may offer novel treatment strategies for IBD patients.
