Histamine H4 receptor knockout mice display reduced inflammation in a chronic model of atopic dermatitis

Background The histamine H4 receptor (H4R) was brought into focus as a new therapeutic target for the treatment of allergic disorders such as atopic dermatitis (AD). H4R antagonists have already been tested in several animal models of AD, but these studies have yielded conflicting results. Material...

Full description

Saved in:

Bibliographic Details
Published in:	Allergy (Copenhagen) Vol. 71; no. 2; pp. 189 - 197
Main Authors:	Rossbach, K., Schaper, K., Kloth, Ch, Gutzmer, R., Werfel, T., Kietzmann, M., Bäumer, W.
Format:	Journal Article
Language:	English
Published:	Denmark Blackwell Publishing Ltd 01-02-2016
Subjects:	Allergic inflammation Allergies Animals atopic dermatitis CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Cytokines - biosynthesis Dermatitis Dermatitis, Atopic - drug therapy Dermatitis, Atopic - etiology Dermatitis, Atopic - metabolism Dermatitis, Atopic - pathology Disease Models, Animal Epidermis - immunology Epidermis - metabolism Epidermis - pathology Female histamine H4 receptor Immunoglobulin E - immunology Inflammation Lymph Nodes - immunology Lymph Nodes - metabolism Mice Mice, Knockout OVA Ovalbumin - adverse effects Piperidines - pharmacology Pyridines - pharmacology Receptors, G-Protein-Coupled - antagonists & inhibitors Receptors, G-Protein-Coupled - deficiency Receptors, G-Protein-Coupled - genetics Receptors, Histamine - deficiency Receptors, Histamine - genetics Receptors, Histamine H4 Rodents Skin - immunology Skin - metabolism Skin - pathology atopic dermatitis Allergic inflammation OVA histamine H4 receptor
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Background The histamine H4 receptor (H4R) was brought into focus as a new therapeutic target for the treatment of allergic disorders such as atopic dermatitis (AD). H4R antagonists have already been tested in several animal models of AD, but these studies have yielded conflicting results. Material and methods The development of ovalbumin‐induced AD‐like skin lesions was analysed in H4R−/− mice and in H4R antagonist (JNJ28307474)‐treated mice. Results H4R−/− mice showed a clear amelioration of the skin lesions, with a diminished influx of inflammatory cells and a reduced epidermal hyperproliferation at lesional skin sites. H4R−/− mice had a reduced amount of ovalbumin‐specific IgE, a reduced number of splenocytes and lymph node cells with a decreased number of CD4+ T cells. The H4R modulated the cytokine secretion of CD4+ T cells and splenocytes and altered the cellular profile in the lymph nodes. The anti‐inflammatory effect could only partially be mimicked by JNJ28307474 and only when the H4R antagonist was given during sensitization and challenge and not when JNJ28307474 was only given during the provocation phase of the allergic reaction. Conclusion The H4R modulates inflammation in a chronic allergic dermatitis setting. However, results of this study indicate that it is necessary to block the H4R during ontogeny and development of the allergic inflammation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0105-4538 1398-9995
DOI:	10.1111/all.12779