Open AccessBalancing intestinal and systemic inflammation through cell type-specific expression of the aryl hydrocarbon receptor repressor
Author(s) -
Olga Brandstätter,
Oliver Schanz,
Julia Vorac,
Jessica König,
Tetsushi Mori,
Toru Maruyama,
Markus Korkowski,
Thomas HaarmannStemmann,
Dorthe von Smolinski,
Joachim L. Schultze,
Josef Abel,
Charlotte Esser,
Haruko Takeyama,
Heike Weighardt
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep26091
Subject(s) - aryl hydrocarbon receptor , immune system , inflammation , repressor , microbiology and biotechnology , chemistry , context (archaeology) , receptor , effector , biology , gene expression , immunology , gene , biochemistry , transcription factor , paleontology
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.