title: Balancing intestinal and systemic inflammation through cell type-specific expression of the aryl hydrocarbon receptor repressor.
abstract: 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.
authors.affiliation: Immunology and Environment, Life and Medical Sciences (LIMES) Institute, University of Bonn, Carl-Troll-Straße 31, 53115 Bonn, Germany.|IUF-Leibniz Research Institute for Environmental Medicine gGmbH, Auf´m Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Brandstätter
authors.affiliation: Immunology and Environment, Life and Medical Sciences (LIMES) Institute, University of Bonn, Carl-Troll-Straße 31, 53115 Bonn, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Schanz
authors.affiliation: Immunology and Environment, Life and Medical Sciences (LIMES) Institute, University of Bonn, Carl-Troll-Straße 31, 53115 Bonn, Germany.|IUF-Leibniz Research Institute for Environmental Medicine gGmbH, Auf´m Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Vorac
authors.affiliation: Immunology and Environment, Life and Medical Sciences (LIMES) Institute, University of Bonn, Carl-Troll-Straße 31, 53115 Bonn, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: König
authors.affiliation: Center for Advanced Biomedical Sciences (TWIns), Waseda University, 2-2, Wakamatsu-cho, Shinjuku-ku, 162-8480, Tokyo, Japan.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Mori
authors.affiliation: Center for Advanced Biomedical Sciences (TWIns), Waseda University, 2-2, Wakamatsu-cho, Shinjuku-ku, 162-8480, Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine gGmbH, Auf´m Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Korkowski
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine gGmbH, Auf´m Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Haarmann-Stemmann
authors.affiliation: Institut für Tierpathologie der FU Berlin, Robert von Ostertag Strasse 15, 14163 Berlin.
authors.forename: Dorthe
authors.initials: D
authors.lastname: von Smolinski
authors.affiliation: Genomics and Immunoregulation, Life and Medical Sciences (LIMES) Institute, University of Bonn, Carl-Troll-Straße 31, 53115 Bonn, Germany.
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine gGmbH, Auf´m Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Abel
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine gGmbH, Auf´m Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Esser
authors.affiliation: Center for Advanced Biomedical Sciences (TWIns), Waseda University, 2-2, Wakamatsu-cho, Shinjuku-ku, 162-8480, Tokyo, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Takeyama
authors.affiliation: Immunology and Environment, Life and Medical Sciences (LIMES) Institute, University of Bonn, Carl-Troll-Straße 31, 53115 Bonn, Germany.|IUF-Leibniz Research Institute for Environmental Medicine gGmbH, Auf´m Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Weighardt
authors.affiliation: Immunology and Environment, Life and Medical Sciences (LIMES) Institute, University of Bonn, Carl-Troll-Straße 31, 53115 Bonn, Germany.|IUF-Leibniz Research Institute for Environmental Medicine gGmbH, Auf´m Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Förster
mesh_terms: D000825:Animal Structures / Q000201:enzymology / Q000473:pathology; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D004751:Enteritis / Q000473:pathology*; D005786:Gene Expression Regulation; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; C484722:Ahr protein, mouse; C117300:Ahrr protein, mouse