Histamine receptor H1 signaling on dendritic cells plays a key role in the IFN-γ/IL-17 balance in T cell-mediated skin inflammation.
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).


OBJECTIVE
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.


CONCLUSIONS
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.
Université de Lyon, Lyon, France.
Béatrice
B
Vanbervliet
Mübeccel
M
Akdis
Marc
M
Vocanson
Aurore
A
Rozières
Josette
J
Benetière
Paul
P
Rouzaire
Cezmi A
CA
Akdis
Jean-François
JF
Nicolas
Ana
A
Hennino
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011969:Receptors, Histamine H1 / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D020381:Interleukin-17; D011969:Receptors, Histamine H1; D007371:Interferon-gamma