title: The aryl hydrocarbon receptor is functionally upregulated early in the course of human T-cell activation.
abstract: The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates immunosuppression caused by a variety of environmental contaminants, such as polycyclic aromatic hydrocarbons or dioxins. Recent evidence suggests that AhR plays an important role in T-cell-mediated immune responses by affecting the polarization and differentiation of activated T cells. However, the regulation of AhR expression in activated T cells remains poorly characterized. In the present study, we used purified human T cells stimulated with anti-CD3 and anti-CD28 Abs to investigate the effect of T-cell activation on AhR mRNA and protein expression. The expression of AhR mRNA increased significantly and rapidly after T-cell activation, identifying AhR as an immediate-early activation gene. AhR upregulation occurred in all of the T-cell subtypes, and is associated with its nuclear translocation and induction of the cytochromes P-450 1A1 and 1B1 mRNA expression in the absence of exogenous signals. In addition, the use of an AhR antagonist or siRNA-mediated AhR knockdown significantly inhibited IL-22 expression, suggesting that expression and functional activation of AhR is necessary for the secretion of IL-22 by activated T cells. In conclusion, our data support the idea that AhR is a major player in T-cell physiology.
authors.affiliation: UMR INSERM U1085, Institut de Recherche sur la Santé, l'Environnement et le Travail (IRSET), Université de Rennes 1, Rennes, France.
authors.forename: Laurie
authors.initials: L
authors.lastname: Prigent
authors.forename: Marc
authors.initials: M
authors.lastname: Robineau
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jouneau
authors.forename: Claudie
authors.initials: C
authors.lastname: Morzadec
authors.forename: Laetitia
authors.initials: L
authors.lastname: Louarn
authors.forename: Laurent
authors.initials: L
authors.lastname: Vernhet
authors.forename: Olivier
authors.initials: O
authors.lastname: Fardel
authors.forename: Lydie
authors.initials: L
authors.lastname: Sparfel
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D002467:Cell Nucleus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D065633:Cytochrome P-450 CYP1B1; D055785:Gene Knockdown Techniques; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology*; D014176:Protein Biosynthesis / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D007378:Interleukins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D000097043:Interleukin-22; C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human
keywords: Aryl hydrocarbon receptor; Human T lymphocytes; T-cell activation