The Histamine H4 Receptor Is Highly Expressed on Plasmacytoid Dendritic Cells in Psoriasis and Histamine Regulates Their Cytokine Production and Migration

Plasmacytoid dendritic cells (pDC) are present in inflammatory skin lesions, in particular, in psoriasis. In such lesions, the inflammatory mediator histamine is also detected in high amounts. We therefore investigated a possible interaction of pDC with histamine, especially via the most recently described histamine H-4 receptor (H4R). We detected the expression of the H4R on pDC in the blood and in lesional psoriasis skin. Interestingly, compared with healthy controls and patients with atopic dermatitis, pDC from the blood of psoriasis patients expressed the highest levels of the H4R, which was even more upregulated on stimulation with IFN-gamma and CpG. After activation of the H2R and H4R on pDC, we observed downregulation of CpG-induced production of tumor necrosis factor alpha, IFN-alpha, and CXCL8, but not of the chemokine CXCL10. Histamine-induced downregulation of cytokine production was more pronounced in pDC derived from psoriasis patients. Furthermore, we observed F-actin polymerization and active migration of pDC in response to H4R agonist stimulation. Taken together, our results indicate that the H4R is highly expressed on pDC in psoriasis and influences cytokine production and migration of pDC. Therefore, the H4R alone or in combination with the H2R might be a promising therapeutic target in psoriasis.