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Vanbervliet, B; Akdis, M; Vocanson, M; Rozières, A; Benetière, J; Rouzaire, P; Akdis, C A; Nicolas, J F; Hennino, A (2011). Histamine receptor H1 signaling on dendritic cells plays a key role in the IFN-γ/IL-17 balance in T cell-mediated skin inflammation. Journal of Allergy and Clinical Immunology, 127(4):943-953.e1.

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BACKGROUND: The diverse effects of histamine on immune regulation are a result of the differential expression and regulation of 4 histamine receptors. Many of the immediate allergic and inflammatory actions of histamine are mediated via the type 1 receptor (H1R). OBJECTIVES: We hypothesized that H1R was involved in the fine-tuning of the initiation of T cell-mediated skin pathology-that is, dermatitis. METHODS: The impact of the H1R invalidation on the development of skin inflammation was analyzed in a mouse model of atopic dermatitis. RESULTS: We show that H1r(-)/(-) mice developed reduced allergen-specific skin lesions. Lack of H1R expression on dendritic cells (DCs) led to diminished IL-12, upregulated IL-23, and IL-6 production upon allergen stimulation. H1R engagement on dendritic cells was necessary for DC activation and subsequent priming of effector IFN-γ(+)CD8(+) T cells. We demonstrate here that H1R blockade on DCs promotes generation of noneffector IL-17(+)CD8(+) T cells that are unable to initiate the skin inflammation. CONCLUSION: Our data identify that histamine signaling through the H1R on DCs is an important early event conditioning the quality of the skin effector immune response. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.


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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Swiss Institute of Allergy and Asthma Research
Dewey Decimal Classification:610 Medicine & health
Deposited On:10 Mar 2012 17:06
Last Modified:27 Nov 2013 16:30
Publisher DOI:10.1016/j.jaci.2010.12.002
PubMed ID:21269673

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