2 research outputs found
Balancing intestinal and systemic inflammation through cell type-specific expression of the aryl hydrocarbon receptor repressor
As a sensor of polyaromatic chemicals the aryl hydrocarbon receptor (AhR)
exerts an important role in immune regulation besides its requirement for
xenobiotic metabolism. Transcriptional activation of AhR target genes is
counterregulated by the AhR repressor (AhRR) but the exact function of the
AhRR in vivo is currently unknown. We here show that the AhRR is predominantly
expressed in immune cells of the skin and intestine, different from other AhR
target genes. Whereas AhRR antagonizes the anti-inflammatory function of the
AhR in the context of systemic endotoxin shock, AhR and AhRR act in concert to
dampen intestinal inflammation. Specifically, AhRR contributes to the
maintenance of colonic intraepithelial lymphocytes and prevents excessive IL-
1β production and Th17/Tc17 differentiation. In contrast, the AhRR enhances
IFN-γ-production by effector T cells in the inflamed gut. Our findings
highlight the physiologic importance of cell-type specific balancing of
AhR/AhRR expression in response to microbial, nutritional and other
environmental stimuli