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Activation of the aryl hydrocarbon receptor reveals distinct requirements for IL-22 and IL-17 production by human T helper cells

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Published in European Journal of Immunology. 2010, vol. 40, no. 9, p. 2450-2459
Abstract Ligands of the aryl hydrocarbon receptor (AHR), a transcription factor mediating the effects of dioxin, favor Th17 differentiation and exacerbate autoimmunity in mice. We investigated how AHR ligands affected human T-cell polarization. We found that the high affinity and stable AHR-ligand dioxin as well as the natural AHR-ligand 6-formylinolo[3,2-b] carbazole induced the downstream AHR-target cytochrome P450A1, and without affecting IFN-gamma, they enhanced IL-22 while simultaneously decreasing IL-17A production by CD4(+) T cells. The specific AHR-inhibitor CH-223191 abolished these effects. Furthermore, blockade of IL-23 and IL-1, important for Th17 expansion, profoundly decreased IL-17A but not IL-22 production. AHR agonists reduced the expression of the Th17 master transcription factor retinoic acid-related orphan receptor C (RORC), without affecting T-bet, GATA-3 and Foxp3. They also decreased the expression of the IL-23 receptor. Importantly, AHR-ligation did not only decrease the number of Th17 cells but also primed naive CD4(+) T cells to produce IL-22 without IL-17 and IFN-gamma. Furthermore, IL-22 single producers did not express CD161, which distinguished them from the CD161(+) Th17 cells. Hence, our data provide compelling evidence that AHR activation participates in shaping human CD4(+) T-cell polarization favoring the emergence of a distinct subset of IL-22-producing cells that are independent from the Th17 lineage.
Keywords Antigens, CD4/biosynthesisAzo Compounds/pharmacologyCarbazoles/pharmacologyCell Differentiation/drug effectsCells, CulturedCytochrome P-450 CYP1A1/metabolismDioxins/pharmacologyHumansInterferon-gamma/immunology/metabolismInterleukin-17/genetics/immunology/*metabolismInterleukins/genetics/immunology/*metabolismLymphocyte Activation/drug effectsNK Cell Lectin-Like Receptor Subfamily B/biosynthesisPyrazoles/pharmacologyReceptors, Aryl Hydrocarbon/immunology/*metabolismT-Lymphocyte Subsets/drug effects/immunology/*metabolism/pathologyT-Lymphocytes, Helper-Inducer/drug effects/immunology/*metabolism/pathologyTranscription Factors/genetics/immunology/metabolismUp-Regulation
PMID: 20706985
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Research groups Analyses cellulaires et moléculaires des hémopathies malignes (929)
La matrice extracellulaire (651)
La recherche en biochimie dermatologique (652)
Rôle du CD44 (809)
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RAMIREZ, Jean-Marie et al. Activation of the aryl hydrocarbon receptor reveals distinct requirements for IL-22 and IL-17 production by human T helper cells. In: European Journal of Immunology, 2010, vol. 40, n° 9, p. 2450-2459. doi: 10.1002/eji.201040461 https://archive-ouverte.unige.ch/unige:21244

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Deposited on : 2012-05-23

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