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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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).
We hypothesized that H1R was involved in the fine-tuning of the initiation of T cell-mediated skin pathology-that is, dermatitis.
The impact of the H1R invalidation on the development of skin inflammation was analyzed in a mouse model of atopic dermatitis.
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.
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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Swiss Institute of Allergy and Asthma Research|
|DDC:||610 Medicine & health|
|Deposited On:||10 Mar 2012 17:06|
|Last Modified:||27 Nov 2013 16:30|
|Citations:||Web of Science®. Times Cited: 9|
Scopus®. Citation Count: 13
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