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Titles listActivation of the aryl hydrocarbon receptor reveals distinct requirements for IL-22 and IL-17 production...
Titles listActivation of the aryl hydrocarbon receptor reveals distinct requirements for IL-22 and IL-17 production...
Scientific Article
unige:21244 
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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/biosynthesis — Azo Compounds/pharmacology — Carbazoles/pharmacology — Cell Differentiation/drug effects — Cells, Cultured — Cytochrome P-450 CYP1A1/metabolism — Dioxins/pharmacology — Humans — Interferon-gamma/immunology/metabolism — Interleukin-17/genetics/immunology/*metabolism — Interleukins/genetics/immunology/*metabolism — Lymphocyte Activation/drug effects — NK Cell Lectin-Like Receptor Subfamily B/biosynthesis — Pyrazoles/pharmacology — Receptors, Aryl Hydrocarbon/immunology/*metabolism — T-Lymphocyte Subsets/drug effects/immunology/*metabolism/pathology — T-Lymphocytes, Helper-Inducer/drug effects/immunology/*metabolism/pathology — Transcription Factors/genetics/immunology/metabolism — Up-Regulation | |
| Identifiers | PMID: 20706985 | |
| Full text |
Article - Limited access to UNIGE Other version: http://onlinelibrary.wiley.com/store/10.1002/eji.201040461/asset/2450_ftp.pdf?v=1&t=h1qhsie6&s=a96e827e94b8e60da94b48... |
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| Structures | ||
| Research groups | Analyses cellulaires et moléculaires des hémopathies malignes (929) La matrice extracellulaire (651) La recherche en biochimie dermatologique (652) Rôle du CD44 (809) | |
| Citation (ISO format) | 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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