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-γ. 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.
