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 goal of a treatment regimen for atopic dermatitis is to reach and maintain a state where the patient exhibits mild symptoms or an absence of symptoms, and the patient should not experience disturbance during daily activities. The basis of a treatment regimen for atopic dermatitis is topical therapy, and currently there exist topical corticosteroids, tacrolimus and delgocitinib. Using these, proactive therapy is performed as maintenance therapy after remission induction therapy. However, in cases of moderate to severe atopic dermatitis, topical drugs alone cannot induce remission and systemic therapies such as cyclosporin, ultraviolet therapy, and dupilumab should be used in combination. In particular, dupilumab has many advantages such as high efficacy, relatively few adverse reactions, and ease of use in elderly patients with severe atopic dermatitis. In this review, we present a treatment algorithm for atopic dermatitis that emphasizes the importance of maintaining remission after induction of remission, and summarizes the characteristics of current medication therapy for atopic dermatitis in Japan.

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We present a case of Panton‐Valentine leucocidin‐positive methicillin‐susceptible Staphylococcus aureus infection in a couple. The isolated bacterium was not methicillin‐resistant but was very closely related to the USA300 clone.

Trans-urocanic acid (UCA) is a natural photoreceptor present in the stratum corneum of the skin. Upon exposure to ultraviolet-radiation (UV-R), trans-UCA is isomerized to cis-UCA. Several studies indicate that cis-UCA induces local and systemic immune suppression via various underlying mechanisms. However, microbes are established all over the surface of the skin and the interplay between cis-UCA and the skin microbiome is not completely understood. In this study, we investigated the effects of cis-UCA on the skin microbiome and antimicrobial peptides (AMPs) expression using mouse models. We employed HPLC to determine quantitative isomerization of trans-UCA to cis-UCA by UV-R. We further made use of the model of contact allergy to assess the percentage of immune suppression by UV-A, UV-B, PUVA and cis-UCA to the contact allergen DNFB. Next, we treated mice with UV-A, UV-B, PUVA and cis-UCA and performed 16S rRNA gene sequencing for microbiome analysis and qPCR for AMPs gene expression. We noted that UV-B (p¼0.002) and PUVA (p¼0.023) significantly increased the formation of cis-UCA, whereas UV-A exposure alone showed no significant formation of cis-UCA in the skin. Utilizing the contact allergy model, we observed a dose-dependent increase in immune suppression (by up to 100%) against the contact allergen DNFB, when mice were pretreated with cis-UCA. Furthermore, application of cis-UCA on the skin altered the microbial landscape of the skin both at 8h and 24h, correlating with a change in expression of various AMPs. Collectively our results suggest that cis-UCA alters the skin microbial landscape and AMP expression. This imbalance in the skin microbial landscape and altered AMP expression may be crucial in immune suppression upon UV-R exposure mediated through cis-UCA.