Inhibitory effect of a histamine 4 receptor antagonist on CCL17 and CCL22 production by monocyte‐derived Langerhans cells in patients with atopic dermatitis

Abstract

We examined the inhibitory effect of a histamine 4 receptor (H4R) antagonist (JNJ7777120) on CCL17 and CCL22 chemokine production by human monocyte-derived Langerhans cells (MoLC) in patients with atopic dermatitis (AD) and healthy controls (HC). We confirmed the significantly higher production of both CCL17 and CCL22 in the MoLC of AD patients compared with HC. The H4R antagonist significantly inhibited the production of both CCL17 and CCL22 in the MoLC of AD patients. With regard to TLR2-signaled enhancement, peptidoglycan (PGN)-enhanced production of CCL17 and CCL22 by MoLC was inhibited by the H4R. Immunoblotting analysis demonstrated that phosphorylated p38 mitogen-activated protein kinase was induced by PGN and that this enhancement was attenuated by the application of the H4R antagonist. These data indicate that H4 signaling modulates the production of T-helper 2 chemokine in MoLC and contributes to chronic inflammation in AD patients. Our data suggest a possible novel therapeutic approach using a H4R antagonist in the treatment of patients with AD.

The role of the histamine H4 receptor in atopic dermatitis and psoriasis

“…By applying the H 4 receptor antagonist JNJ‐7777120, Miyano et al . () demonstrated that these receptors were responsible for enhanced spontaneously or peptidoglycan‐induced production of CCL17 and as opposed to our study also of CCL22 production in monocyte‐derived LCs in patients with AD.…”

Molecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis

“…The levels of CCL17 and CCL22 may reflect the degree of skin barrier impairment. CCL17 and CCL22 induce the skin homing of T cells into AD lesions, and H4R antagonist inhibits CCL17 and CCL22 chemokine production by LCs in patients with AD [184]. Cutaneous T cell-attracting chemokine, also known as CCL27, is produced by keratinocytes and attracts CCR10-expressing Th22 cells into the skin.…”

Histamine, histamine receptors, and anti-histamines in the context of allergic responses

“…H 4 receptor agonists have been shown to suppress CCL2 mRNA expression in monocyte-derived Langerhans cells, and induce the migration of Langerhans cells from the epidermis (Gschwandtner et al 2010). The application of H 4 receptor antagonists in studies showed significant inhibition of CCL17 and CCL22 production by monocytes of patients with atopic dermatitis, with only marginal effects in healthy individuals (Miyano et al 2016). Since the application of H 1 and H 4 receptor antagonists decreases pruritus in atopic dermatitis, the H 4 receptor has also been linked to pruritus development (Ohsawa and Hirasawa 2012;Köchling et al 2017).…”