TY - JOUR
T1 - Balancing intestinal and systemic inflammation through cell type-specific expression of the aryl hydrocarbon receptor repressor
AU - Brandstätter, Olga
AU - Schanz, Oliver
AU - Vorac, Julia
AU - König, Jessica
AU - Mori, Tetsushi
AU - Maruyama, Toru
AU - Korkowski, Markus
AU - Haarmann-Stemmann, Thomas
AU - Von Smolinski, Dorthe
AU - Schultze, Joachim L.
AU - Abel, Josef
AU - Esser, Charlotte
AU - Takeyama, Haruko
AU - Weighardt, Heike
AU - Förster, Irmgard
N1 - Funding Information:
We are grateful to Nicole Küpper, Sandra Beer and Klaus Pfeffer for discussion and technical help in the generation of AhRR/EGFP mice. We thank Gabriele Schoder, Ingo Uthe, Björn Zapke and Philip Hatzfeld for expert technical assistance. This work was supported by the Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU-B5) (to I.F. and J.A.), the Deutsche Forschungsgemeinschaft through SFB704, GK1427, the Stiftung zur Erforschung infektiös-immunologischer Erkrankungen (to I.F.), the Jürgen-Manchot-Stiftung through the graduate school MOI (to H.W. and I.F.), and the Leibnizgemeinschaft by Leibniz Competition (to H.W. and I.F.). I.F. and J.L.S are members of the Bonn Cluster of Excellence "ImmunoSensation".
Publisher Copyright:
© 2016, Nature Publishing Group. All rights reserved.
PY - 2016/5/17
Y1 - 2016/5/17
N2 - 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.
AB - 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.
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U2 - 10.1038/srep26091
DO - 10.1038/srep26091
M3 - Article
C2 - 27184933
AN - SCOPUS:84968784351
SN - 2045-2322
VL - 6
JO - Scientific reports
JF - Scientific reports
M1 - 26091
ER -