1. ¹Department of Dermatology and Allergology, Hannover Medical School, Hannover, Germany
2. ²Institute for Pharmaceutical Chemistry, Biozentrum ZAFES/CMP, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany
3. ³Centre for Integrative Neuroscience, Durham University, School of Biological and Biomedical Sciences, Durham, UK
4. ⁴Department of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

Correspondence: Dorothea Dijkstra, Correspondence: Dr Dorothea Dijkstra, Department of Dermatology and Allergology, Hannover Medical School, Ricklinger Strasse 5, Hannover D-30449, Germany. E-mail: dijkstra.dorothea@mh-hannover.de

Received 31 May 2007; Revised 1 November 2007; Accepted 29 November 2007; Published online 31 January 2008.

Abstract

Expression of histamine H₄ receptor (H₄R) on leukocytes suggests an immunomodulatory role of this receptor. Here we investigated the expression and function of H₄R on human inflammatory dendritic epidermal cells (IDECs). H₄R is expressed by IDEC of the skin. On monocyte-derived IDECs (Mo-IDECs), H₄R is also expressed and upregulated by IFN-. Functionally, histamine and H₄R agonists clobenpropit and 4-methylhistamine downregulated the production of the Th2-linked chemokine CCL2 and the Th1 cytokine IL-12 on Mo-IDEC, whereas agonists for the other histamine receptors did not. An H₄R-selective antagonist (JNJ7777120) blocked the effect of H₄R agonists. Downregulation of CCL2 also led to a decreased migration of monocytes. Thus, IDEC express a functionally active H₄R, which upon stimulation leads to downregulation of CCL2 and IL-12. This might have implications for the treatment of atopic dermatitis, since H₄R agonists may have beneficial effects in downregulating inflammation.