UNIGE document Scientific Article
previous document  unige:21244  next document
add to browser collection
Title

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

Authors show hidden authors show all authors [1 - 9]
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
Identifiers
PMID: 20706985
Full text
Structures
Research groups La matrice extracellulaire (651)
La recherche en biochimie dermatologique (652)
Rôle du CD44 (809)
Analyses cellulaires et moléculaires des hémopathies malignes (929)
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. https://archive-ouverte.unige.ch/unige:21244

185 hits

0 download

Update

Deposited on : 2012-05-23

Export document
Format :
Citation style :