Abstract
Histamine4 receptor (H4R) is a member of the histamine receptors which exists on Th17 cells, NK cells, keratinocytes and dendritic cells. H4R was recently demonstrated to be functionally expressed on Langerhans cells (LCs), while H4 signaling was found to participate in the itch response. We performed in vitro experiments to investigate the production of CCL17 and CCL22 production by MoLCs. We next examined the effects of an H4R antagonist (JNJ7777120) on the production of Th2 chemokines by the MoLCs of atopic dermatitis (AD) patients. We examined the inhibitory effect of the H4R antagonist on the production of CCL17 and CCL22 by the MoLCs of AD patients. The application of the H4R antagonist significantly inhibited the production of both the CCL17 and CCL22 chemokines by MoLCs of AD patients. We examined the inhibitory effect of the H4R antagonist on PGN-stimulated CCL17 and CCL22 production by the MoLCs of AD patients. We detected inhibitory effect of H4R antagonist on CCL17 and CCL22 production by PGN-treated MoLCs. Significant inhibitory effects were observed at 33nM concentration for the chemokine production. We demonstrated the following new findings. First, an H4R antagonist (JNJ7777120) inhibited CCL17 and CCL22 production by the MoLCs of AD patients. Next the PGN-induced chemokine production in AD patients was suppressed by the H4R antagonists. Finally, the H4R antagonist inhibited the PGN-induced phosphorylated p38 MAP kinase activity in the MoLCs of AD patients. We also confirmed the enhancement of CCL17 and CCL22 production by the MoLCs of AD patients in comparison to HCs. Our data demonstrate, for the first time, that an H4R antagonist significantly inhibited the CCL17 and CCL22 production by the MoLCs of AD patients. Thus, our data strongly suggest that H4R signals can modulate Th2 cells recruitment in the lesional skin of AD patients.
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