title: The Aryl hydrocarbon receptor is involved in UVR-induced immunosuppression.
abstract: UVR suppresses the immune system through the induction of regulatory T cells (Tregs). UVR-induced DNA damage has been recognized as the major molecular trigger involved, as reduction of DNA damage by enhanced repair prevents the compromise to the immune system by UVR. Nevertheless, other signaling events may also be involved. The aryl hydrocarbon receptor (AhR) was identified as another target for UVR, as UVR activates the AhR and certain UVR effects were not detected in AhR-deficient cells. We studied whether the AhR is involved in UVR-induced local immunosuppression and whether similar effects can be induced by AhR agonists. The AhR antagonist 3-methoxy-4-nitroflavone reduced UVR-mediated immunosuppression and the induction of Tregs in murine contact hypersensitivity (CHS). Conversely, activation of the AhR by the agonist 4-n-nonylphenol (NP) suppressed the induction of CHS and induced antigen-specific Tregs similar to UVR. This was further confirmed in AhR knockout mice in which UVR- and NP-induced immunosuppression were significantly reduced. Together, this indicates that the AhR is involved in mediating UVR-induced immunosuppression. Activation of the AhR might represent an alternative to modulate the immune system in a similar manner like UVR but without causing the adverse effects of UVR, including DNA damage.
authors: Department of Dermatology, University Kiel, Kiel, Germany.
authors: Fatemeh
authors: F
authors: Navid
authors: Department of Dermatology, University Kiel, Kiel, Germany.
authors: Anika
authors: A
authors: Bruhs
authors: Department of Dermatology, University Kiel, Kiel, Germany.
authors: Winfried
authors: W
authors: Schuller
authors: Institut für Umweltmedizinische Forschung (IUF), Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
authors: Ellen
authors: E
authors: Fritsche
authors: Institut für Umweltmedizinische Forschung (IUF), Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
authors: Jean
authors: J
authors: Krutmann
authors: Department of Dermatology, University Kiel, Kiel, Germany. Electronic address: tschwarz@dermatology.uni-kiel.de.
authors: Thomas
authors: T
authors: Schwarz
authors: Department of Dermatology, University Kiel, Kiel, Germany.
authors: Agatha
authors: A
authors: Schwarz
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000276:immunology; D004249:DNA Damage; D003713:Dendritic Cells / Q000276:immunology; D003877:Dermatitis, Contact; D005260:Female; D005419:Flavonoids / Q000737:chemistry; D007108:Immune Tolerance / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010636:Phenols / Q000737:chemistry; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014466:Ultraviolet Rays
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005419:Flavonoids; D010636:Phenols; D018336:Receptors, Aryl Hydrocarbon; C091768:3'-methoxy-4'-nitroflavone; C484722:Ahr protein, mouse; C041594:4-nonylphenol