Murine and human Langerhans cells express a functional histamine H4 receptor: modulation of cell migration and function

Abstract

Histamine is an important mediator of allergic reactions, and recent studies indicated that the function of different types of antigen presenting cells (APC) can be modulated by histamine, in particular via the newly described histamine H(4) receptor (H(4)R). Therefore, we investigated possible interactions of histamine via the H(4)R on Langerhans cells (LC), which represent the professional APC in the skin and therefore have an important role in the initiation and maintenance of allergic skin diseases. The expression of the H(4)R was evaluated by real-time PCR, flow cytometry and immunofluorescence staining. The function of the H(4)R was determined by intracellular flow cytometric measurement of chemokine production and LC migration assays. Here, we show H(4)R expression on in vitro generated monocyte-derived LC (mRNA and protein) and on primary LC from murine and human skin samples (protein). The immunofluorescence staining in murine and human skin samples clearly proved that LC express the H(4)R in situ. Stimulation with histamine or a H(4)R agonist downregulated the chemokine (C-C motif) ligand 2 (CCL2) in human monocyte-derived LC and primary LC. Prestimulation with a selective H(4)R antagonist abolished this effect. Moreover, migration of LC from the epidermis was increased after H(4)R agonist stimulation in ex vivo migration assays using human epidermis and murine in vivo assays. Our findings show that LC express a functional H(4)R and point towards a possible pathogenic relevance of the H(4)R in inflammatory and allergic diseases.