Impact of fucosyltransferase 1-mediated epidermal blood group antigen H on anti-inflammatory response in atopic dermatitis.

The presence of the blood group H2 antigen on the membrane of red blood cells determines blood type O in individuals and this H2 antigen serves as a precursor to the A and B antigens expressed in blood types A and B, respectively. However, the specific involvement of ABH antigens in skin diseases is unknown. Therefore, we aim to investigate the expression of ABH antigens in skin tissue of patients with atopic dermatitis (AD) and MC903-induced AD-like mice. We demonstrated that the expression of ABH antigen is primarily located in the granular and horny layers of the skin in healthy control individuals. However, in patients with AD, the expression of the ABH antigen was absent or diminished in these layers, while the H2 antigen expression increased in the spinous layers of the affected skin lesions. Then, we investigated the biological function of blood group H antigen mediated by fucosyltransferase 1 (Fut1) in the skin, utilizing an AD mouse model induced by MC903 in wild-type (WT) and Fut1-knockout mice. After the application of MC903, Fut1-deficient mice, with no H2 antigen expression on their skin, exhibited more severe clinical signs, increased ear swelling, and elevated serum IgE levels compared with those of WT mice. Additionally, the MC903-induced thickening of both the epidermis and dermis was more pronounced in Fut1-deficient mice than that in WT mice. Furthermore, Fut1-deficient mice showed a significantly higher production of interleukin-4 (IL-4) and IL-6 in skin lesions compared with that of their WT counterparts. The expression of chemokines, particularly Ccl2 and Ccl8, was notably higher in Fut1-deficient mice compared with those of WT mice. The infiltration of CD4+ T cells, eosinophils, and mast cells into the lesional skin was significantly elevated in Fut1-deficient mice compared with that in WT mice. These findings demonstrate the protective role of H2 antigen expression against AD-like inflammation and highlight its potential therapeutic impact on AD through the regulation of blood group antigens.

Higher Expression of Lympho-epithelial Kazal-type-Related Inhibitor-1 Fragments and Decreased Desquamation in the Lesional Skin of Nummular Eczema.

Nummular eczema, a chronic dermatitis characterized by coin-shaped lesions, was first documented in 1857. However, its pathophysiological characteristics are still not well known. To investigate differences in the regulation of the desquamation process in the stratum corneum of lesional and nonlesional skin of patients with nummular eczema and healthy control subjects, tape-stripped stratum corneum samples from patients with nummular eczema and healthy volunteers were analysed using immunofluorescence staining and western blot analysis. In the nummular eczema lesional skin, expression of desmoglein-1, desmocollin-1, and corneodesmosin exhibited a disorganized, dense or partially diffuse non-peripheral pattern with increased intensity, compared with the peripheral patterns observed in healthy or nonlesional skin, suggesting the impaired desquamation process in nummular eczema. Furthermore, although the expression of the desquamation-related serine proteases, kallikrein-related peptidase 7 and 5, was increased in nummular eczema lesional skin, the immunofluorescence staining of lympho-epithelial Kazal-type-related inhibitor-1, an endogenous inhibitor of various kallikrein-related peptidases, and its fragments were significantly increased in the nummular eczema lesional skin, suggesting its contribution to the inhibition of corneodesmosomal degradation. Therefore, the increased detection of corneodesmosomal proteins in nummular eczema lesions may be due to the increased amount of the fragments of lympho-epithelial Kazal-type-related inhibitor-1, which could contribute to delayed desquamation.

Fucosylation deficiency enhances imiquimod-induced psoriasis-like skin inflammation by promoting CXCL1 expression.

Psoriasis is a multifaceted chronic inflammatory skin disease; however, its underlying molecular mechanisms remain unclear. In this study, we explored the role of fucosylation in psoriasis using an imiquimod-induced psoriasis-like mouse model. ABH antigen and fucosyltransferase 1 (Fut1) expression was reduced in the granular layer of lesional skin of patients with psoriasis. In particular, the blood group H antigen type 2 (H2 antigen)-a precursor of blood group A and B antigens-and FUT1 were highly expressed throughout the spinous layer in both patients with psoriasis and the skin of imiquimod-treated mice. Upon the application of imiquimod, Fut1-deficient mice, which lacked the H2 antigen, exhibited higher clinical scores based on erythema, induration, and scaling than those of wild-type mice. Imiquimod-treated Fut1-deficient mice displayed increased skin thickness, trans-epidermal water loss, and Gr-1+ cell infiltration compared with wild-type mice. Notably, the levels of CXCL1 protein and mRNA were significantly higher in Fut1-deficient mice than those in wild-type mice; however, there were no significant differences in other psoriasis-related markers, such as IL-1ß, IL-6, IL-17A, and IL-23. Fut1-deficient primary keratinocytes treated with IL-17A also showed a significant increase in both mRNA and protein levels of CXCL1 compared with IL-17A-treated wild-type primary keratinocytes. Further mechanistic studies revealed that this increased Cxcl1 mRNA in Fut1-deficient keratinocytes was caused by enhanced Cxcl1 mRNA stabilization. In summary, our findings indicated that fucosylation, which is essential for ABH antigen synthesis in humans, plays a protective role in psoriasis-like skin inflammation and is a potential therapeutic target for psoriasis.

Functionally similar genes exhibit comparable/similar time-course expression kinetics in the UV-induced photoaged mouse model.

Skin photoaging induced by ultraviolet (UV) irradiation contributes to the formation of thick and coarse wrinkles. Humans are exposed to UV light throughout their lives. Therefore, it is crucial to determine the time-sequential effects of UV on the skin. In this study, we irradiated the mouse back skin with UV light for eight weeks and observed the changes in gene expressions via microarray analysis every week. There were more downregulated genes (514) than upregulated genes (123). The downregulated genes had more functional diversity than the upregulated genes. Additionally, the number of downregulated genes did not increase in a time-dependent manner. Instead, time-dependent kinetic patterns were observed. Interestingly, each kinetic cluster harbored functionally enriched gene sets. Since collagen changes in the dermis are considered to be a major cause of photoaging, we hypothesized that other gene sets contributing to photoaging would exhibit kinetics similar to those of the collagen-regulatory genes identified in this study. Accordingly, co-expression network analysis was conducted using 11 well-known collagen-regulatory seed genes to predict genes with similar kinetics. We ranked all downregulated genes from 1 to 504 based on their expression levels, and the top 50 genes were suggested to be involved in the photoaging process. Additionally, to validate and support our identified top 50 gene lists, we demonstrated that the genes (FN1, CCDC80, PRELP, and TGFBR3) we discovered are downregulated by UV irradiation in cultured human fibroblasts, leading to decreased collagen levels, which is indicative of photoaging processes. Overall, this study demonstrated the time-sequential genetic changes in chronically UV-irradiated skin and proposed 50 genes that are involved in the mechanisms of photoaging.

Adiponectin-derived pentapeptide ameliorates psoriasiform skin inflammation by suppressing IL-17 production in γδT cells.

BACKGROUND: Psoriasis is a common immunologic chronic skin disease that affects at least 100 million individuals worldwide. Adiponectin is associated with psoriasis and suppresses psoriasiform inflammation. Recently, a small-sized transdermally deliverable 5-mer peptide (GLYYF; P5) was discovered as a potential adiponectin receptor 1 agonist. OBJECTIVES: To confirm reduction in adiponectin protein level in the human skin and investigate whether functional adiponectin replenishment by topical P5 application improves psoriasiform skin inflammation. METHODS: Adiponectin protein expression in the skin of individuals with psoriasis and normal skin was examined by immunofluorescence staining. Imiquimod-induced psoriasis-like skin inflammation was induced in wild-type (WT) and adiponectin-deficient (Adipoq-/-) mice. Vehicle and P5 were topically applied to the back skin and ears of mice. Histological study, reverse-transcription quantitative polymerase chain reaction, multiplex-bead array assay, and flow cytometric analysis were performed. RESULTS: Adiponectin protein expression was downregulated both in the epidermis and dermis of psoriatic lesions as compared to that in the normal skin. Topically applied P5 attenuated the severity of imiquimod-induced psoriatic dermatitis in both WT and Adipoq-/- mice by decreasing the expression of psoriasis-related cytokines (Il17a, Il1b, Il6, and Tnfa). P5 application significantly reduced the proportion of interleukin-17A-producing γδT cells. CONCLUSION: Transdermally deliverable adiponectin receptor 1 agonist, P5, can be a potential peptide drug to manage psoriasis by mediating the anti-psoriatic effect of adiponectin.

Efficacy of bleomycin application on periungual warts after treatment with ablative carbon dioxide fractional laser: a pilot study.

Background: Treating periungual warts is a therapeutic challenge. Treatments are often ineffective and may cause complications including permanent nail changes, pain, and scaring. Translesional bleomycin delivery via the multipuncture technique is now reported.Objective: To investigate the efficacy and safety of bleomycin solution (1 U/mL) after ablative fractional carbon dioxide (CO2) laser for treating periungual warts.Methods: Warts were treated with ablative CO2 fractional laser, after which bleomycin was applied. Patients were treated every 2 weeks until the lesions disappeared. Treatment was discontinued if adverse events occurred or the patient wanted to stop.Results: Seventeen patients (11 women, mean age 16.23 years) with a total of 38 warts were enrolled from May 2017 to Aug 2018. Twenty-six lesions (68.4%) achieved complete clearance; three (7.8%) had excellent partial response (>75% improvement). The warts clearing completely did not recur over the follow-up period of 6 months. No significant long-term adverse effects occurred. One lesion showed postinflammatory hyperpigmentation, resolving within 1 month; five patients (29%) had short-term localized moderate pain after treatment.Conclusions: Bleomycin solution after ablative fractional CO2 laser is effective and safe to treat periungual warts. Further large controlled studies are necessary to validate effectiveness and find an optimal regimen.

A case of latanoprost-induced diffuse facial skin hyperpigmentation.

INTRODUCTION: Latanoprost is a prostaglandin F2α analogue, which has been used as a first-line drug for open-angle glaucoma. Common side effects of latanoprost include hyperpigmentation. While it usually occurs on irides or periocular skin, diffuse facial hyperpigmentation is rarely reported. CASE PRESENTATION: A 71-year-old woman was presented with diffuse gray-brown colored maculopatches on her face. The symptom appeared 1 week after she started to use latanoprost eye drops for glaucoma. Biopsy specimen revealed vacuolar degeneration of dermo-epidermal junction and pigment incontinence in dermis. OBJECTIVE: The aim of this paper is to introduce a rare adverse effect of latanoprost and effective way of treatment. METHODS: We stopped her from using latanoprost. She was also treated with 532-nm potassium titanyl phosphate laser and low-fluence 1064-nm Q-switched Nd:YAG laser, while using topical agents. RESULT: After 10 weeks, we observed hyperpigmentation of her face was effectively and safely treated. The patient was satisfied with the result. CONCLUSION: Diffuse facial pigmentation could be one of the latanoprost-induced adverse effects and the laser treatments with topical agents we used can make it improve faster.

A case of multinucleate cell angiohistiocytoma in a 14-year-old boy showing two different clinical and histopathological findings.

Multinucleate cell angiohistiocytoma (MCAH) is a rare cutaneous disease entity characterized by multiple red-to-brown or violaceous papules usually located on the acral regions, such as the face and the distal arms and legs. It affects elderly women more than men and rarely occurs at a young age. The exact pathogenic mechanism of MCAH is not yet clearly understood. We report an exceptionally rare case of a 14-year-old boy who presented with multiple asymptomatic erythematous papules and a single flat brownish plaque on the left chest. The brownish plaque lesion histologically showed proliferation of dilated small vessels in the upper-mid dermis and numerous oddly shaped multinucleate cells intermingled with lymphocytes and macrophages. The erythematous papules also showed dilated small vessels in the upper-mid dermis and multiple interstitial histiocytic infiltrations, but no multinucleate cells were detected. In immunohistochemistry studies, CD68 and vimentin staining were positive for both specimens. Based on the clinicopathological findings and immunohistochemistry studies, MCAH was diagnosed. To the best of our knowledge, this is the first case report of MCAH occurring in young age and showing two different clinical and histological phases at the same time.