title: Aryl hydrocarbon receptor activation affects the dendritic cell phenotype and function during allergic sensitization.
abstract: Aryl hydrocarbon receptor (AhR) activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppresses peanut sensitization by affecting T cell subsets. However, effects of AhR activation on dendritic cells (DC) in an allergic setting were not investigated yet. Therefore, we analysed the effects of AhR activation on DC phenotype in vivo, as well as their ex vivo potency to stimulate allergen-specific splenic T cells and to induce CD4+CD25+Foxp3+ regulatory (T(reg)) cells. C3H/HeOuJ mice were treated with TCDD by gavage and subsequently sensitized to peanut extract (PE). After eight days, mice were sacrificed and DC in spleen and mesenteric lymph nodes (MLN) were characterized or cocultured with PE-specific CD4+ T cells. AhR activation almost doubled the absolute number of CD11c+CD103+ DC, while not affecting CD11b+ DC, the absolute number of DC, the expression of the activation makers MHCII, CD86, CD80, CD40, CD54 and CD8 on CD11c+ and the activation status of CD11c+CD103+ DC in the spleen. In the MLN, TCDD decreased the absolute number of DC and CD103+ DC, while not affecting CD11b+ DC and the expression of activation markers on DC. PE-pulsed splenic DC from TCDD-treated mice suppressed IL-5, IL-13 and IFN-γ production by PE-specific T cells, but did not induce CD4+CD25+Foxp3+ T(reg) cells. This suppression of cytokine production was not mediated by the TCDD-induced increase in CD103+ DC in the spleen. Combined, these results indicate that AhR activation suppresses the initiation of food allergic responses by affecting DC and their interaction with effector T cells.
authors: Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80177, 3508 TD Utrecht, The Netherlands.
authors: V J
authors: VJ
authors: Schulz
authors: M
authors: M
authors: van Roest
authors: M
authors: M
authors: Bol-Schoenmakers
authors: M B M
authors: MB
authors: van Duursen
authors: M
authors: M
authors: van den Berg
authors: R H H
authors: RH
authors: Pieters
authors: J J
authors: JJ
authors: Smit
mesh_terms: D000818:Animals; D010367:Arachis / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006967:Hypersensitivity / Q000276:immunology; D007114:Immunization; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D021183:Peanut Hypersensitivity / Q000276:immunology*; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D015415:Biomarkers; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon