Publications by authors named "Shinsuke Nakazawa"

11 Publications

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Three-dimensional histological explanation of the dermoscopy patterns in acral melanocytic lesions.

J Dermatol 2021 Apr 27. Epub 2021 Apr 27.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Dermoscopic images of pigmented lesions have distinct features on the sole where skin ridges and furrows exist. Pigmentation of benign nevus usually locates on the skin furrow, while the malignant melanoma is pigmented on the skin ridge. Correspondence between dermoscopy and pathology in the pigmented lesions on soles have been studied based on conventional vertical pathological images. However, for the full understanding of the correspondence, observation of horizontal histological images would be required, because the epidermis constructs unique horizontal structures, namely crista profunda limitans, crista profunda intermedia, and transverse ridge. In this study, we analyzed basic dermoscopic images of the representative acral melanocytic lesions (nevus, lentigo, and malignant melanoma) by horizonal histological images. We created serial horizontal pathological images by digital reconstruction of a hundred of serial vertical images. We could show that parallel furrow pattern is created by the pigmentation of crista profunda limitans, parallel ridge pattern by the pigmentation of both of crista profunda limitans and crista profunda intermediate, and lattice-like pattern by the pigmentation of transverse ridge. Our results would be useful for the intuitive histological understanding of dermoscopy.
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http://dx.doi.org/10.1111/1346-8138.15907DOI Listing
April 2021

Immunological Properties of Atopic Dermatitis-Associated Alopecia Areata.

Int J Mol Sci 2021 Mar 5;22(5). Epub 2021 Mar 5.

Department of Cellular & Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.

Alopecia areata (AA) is regarded as a tissue-specific and cell-mediated autoimmune disorder. Regarding the cytokine balance, AA has been considered a type 1 inflammatory disease. On the other hand, AA often complicates atopic dermatitis (AD) and AD is regarded as type 2 inflammatory disease. However, the immunological aspects of AA in relation to AD are still poorly understood. Therefore, we aim to clarify the immunological properties of AD-associated AA. In this study, we performed comparative analysis of the expression of intracytoplasmic cytokines (IFN-γ, IL-4, and IL-13), chemokine receptors (CXCR3 and CCR4) in peripheral blood which were taken from healthy controls, non-atopic AA patients, AA patients with extrinsic AD, and AA patients with intrinsic AD by flowcytometric analysis. We also compared the scalp skin samples taken from AA patients with extrinsic AD before and after treatment with dupilumab. In non-atopic AA patients, the ratios of CD4+IFN-γ+ cells to CD4IL-4 cells and CD4IFN-γ cells to CD4IL-13 cells were higher than those in AA patients with extrinsic AD. Meanwhile, the ratio of CD8IFN-γ cells to CD8+IL-13+ cells was significantly higher in the non-atopic AA than in the healthy controls. In AA patients with extrinsic AD, the skin AA lesion showed dense infiltration of not only CXCR3+ cells but also CCR4 cells around hair bulb before dupilumab treatment. However, after the treatment, the number of CXCR3 cells had no remarkable change while the number of CCR4 cells significantly decreased. These results indicate that the immunological condition of AA may be different between atopic and non-atopic patients and between extrinsic and intrinsic AD patients. Our study provides an important notion that type 2 immunity may participate in the development of AA in extrinsic AD patients. It may be considered that the immunological state of non-atopic AA is different from that of atopic AA.
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http://dx.doi.org/10.3390/ijms22052618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961331PMC
March 2021

Suprabasin-null mice retain skin barrier function and show high contact hypersensitivity to nickel upon oral nickel loading.

Sci Rep 2020 09 3;10(1):14559. Epub 2020 Sep 3.

Department of Dermatology, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-Ku, Hamamatsu, 431-3192, Japan.

Suprabasin (SBSN) is expressed not only in epidermis but also in epithelial cells of the upper digestive tract where metals such as nickel are absorbed. We have recently shown that SBSN level is decreased in the stratum corneum and serum of atopic dermatitis (AD) patients, especially in intrinsic AD, which is characterized by metal allergy. By using SBSN-null (Sbsn) mice, this study was conducted to investigate the outcome of SBSN deficiency in relation to AD. Sbsn mice exhibited skin barrier dysfunction on embryonic day 16.5, but after birth, their barrier function was not perturbed despite the presence of ultrastructural changes in stratum corneum and keratohyalin granules. Sbsn mice showed a comparable ovalbumin-specific skin immune response to wild type (WT) mice and rather lower contact hypersensitivity (CHS) responses to haptens than did WT mice. The blood nickel level after oral feeding of nickel was significantly higher in Sbsn mice than in WT mice, and CHS to nickel was elevated in Sbsn mice under nickel-loading condition. Our study suggests that the completely SBSN deficient mice retain normal barrier function, but harbor abnormal upper digestive tract epithelium that promotes nickel absorption and high CHS to nickel, sharing the features of intrinsic AD.
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http://dx.doi.org/10.1038/s41598-020-71536-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471289PMC
September 2020

Understanding the significance of cytokines and chemokines in the pathogenesis of alopecia areata.

Exp Dermatol 2020 08 3;29(8):726-732. Epub 2020 Jul 3.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Alopecia areata has basically been understood as a type 1 inflammatory disease. Activated NKG2D CD8 cells produce the Th1 cytokine interferon-γ, which leads to the disruption of immune tolerance of hair follicles and the exposure of self-antigens. This results in dense inflammatory cell infiltration and apoptosis around hair follicles, inducing hair loss. A well-known complication of alopecia areata is atopic dermatitis, a typical type 2 inflammatory disease. Hair scientists have shied away from confronting and understanding how alopecia areata, a type 1 inflammatory disease, and atopic dermatitis, a type 2 inflammatory disease, can occur together. This review summarizes the research on the cytokine balance in alopecia areata and then focuses on the classification of the cytokine balance in alopecia areata, including the classification of atopic dermatitis into extrinsic and intrinsic types. Dupilumab reportedly showed dual efficacy in a patient with concomitant atopic dermatitis and alopecia areata, supporting our own experience. Elevated Th2 cytokine levels have also been reported in patients with alopecia areata, with increased serum IL-4, IL-5, IL-6 levels, high IgE levels and elevated eosinophil levels. Because local immunotherapy is a treatment that induces Th2-type inflammation, it may worsen the condition of alopecia areata patients with extrinsic atopic dermatitis. It is desirable to select appropriate treatments with consideration of the cytokine balance.
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http://dx.doi.org/10.1111/exd.14129DOI Listing
August 2020

Protective role of Galectin-7 for skin barrier impairment in atopic dermatitis.

Clin Exp Allergy 2020 08 14;50(8):922-931. Epub 2020 Jun 14.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Background: Atopic dermatitis (AD) patients have a barrier disorder in association with Th2 dominant skin inflammation. Galectin-7 (Gal-7), a soluble unglycosylated lectin, is highly expressed in the stratum corneum of AD patients. However, the biological significance of increased Gal-7 expression in AD skin lesions remains unclear.

Objective: We aimed to investigate the production mechanism and functional role of Gal-7 in AD patients and IL-4/IL-13-stimulated epidermal keratinocytes.

Methods: We assessed the Gal-7 expression levels in skin lesions and sera from AD patients. Gal-7 levels were also measured in monolayered normal human epidermal keratinocytes (NHEKs) and 3-dimensional (3D)-reconstructed epidermis in the presence or absence of IL-4/IL-13 with or without Stat3, Stat6 or Gal-7 gene silencing.

Results: Gal-7 was highly expressed in the stratum corneum or intercellular space of AD lesional epidermis as assessed by the stratum corneum proteome analysis and immunohistochemistry. A positive correlation was noted between serum Gal-7 level and transepidermal water loss in patients with AD. These clinical findings were corroborated by our in vitro data, which showed that IL-4/IL-13 facilitated the extracellular release of endogenous Gal-7 in both monolayered NHEKs and 3D-reconstructed epidermis. This machinery was caused by IL-4/IL-13-induced cell damage and inhibited by knockdown of Stat6 but not Stat3 in NHEKs. Moreover, we performed Gal-7 knockdown experiment on 3D-reconstructed epidermis and the result suggested that endogenous Gal-7 serves as a protector from IL-4/IL-13-induced disruption of cell-to-cell adhesion and/or cell-to-extracellular matrix adhesion.

Conclusion And Clinical Relevance: Our study unveils the characteristic of Gal-7 and its possible role as an alarmin that reflects the IL-4/IL-13-induced skin barrier impairment in AD.
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http://dx.doi.org/10.1111/cea.13672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496409PMC
August 2020

Decreased expression of suprabasin induces aberrant differentiation and apoptosis of epidermal keratinocytes: Possible role for atopic dermatitis.

J Dermatol Sci 2019 Sep 27;95(3):107-112. Epub 2019 Jul 27.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address:

Background: Suprabasin (SBSN), a secreted protein, is expressed in various epithelial tissues. The role of SBSN in epidermal differentiation and atopic dermatitis (AD) pathology remains largely unknown.

Objective: To evaluate the effects of SBSN on epidermal keratinocytes and its role in AD.

Methods: We examined the SBSN expression levels in the stratum corneum and the epidermis by proteome analysis and immunohistochemistry, respectively. The serum SBSN concentration was measured by ELISA. These values were compared between AD and healthy control. Morphological changes in the epidermis were investigated in SBSN-knockdown three-dimensional human living skin equivalent (LSE) model with or without IL-4/IL-13.

Results: Epidermal SBSN expression was decreased in AD lesional skin compared to healthy skin, as assessed by the stratum corneum proteome analysis and immunohistochemistry. The SBSN serum levels were significantly lower in AD patients than in normal subjects (P<0.05). The SBSN-deficient LSE exhibited compact stratum corneum, immature stratum granulosum, and increased keratinocyte apoptosis. Th2 cytokines, IL-4 and IL-13, did not affect SBSN expression in LSE. There were no differentiation-associated makers that were affected by the SBSN knockdown. SBSN deficiency-induced apoptosis of keratinocytes was exaggerated by IL-4/IL-13, and accordingly, the addition of recombinant SBSN induced significant keratinocyte proliferation (P<0.05).

Conclusion: Our data demonstrated that SBSN regulates normal epidermal barrier. Th2 cytokines unaffect SBSN expression in keratinocytes, but promote SBSN deficiency-induced apoptosis. It is suggested that SBSN has an anti-apoptotic activity, and its deficiency is involved in the pathogenesis of AD.
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http://dx.doi.org/10.1016/j.jdermsci.2019.07.009DOI Listing
September 2019

Congenital nail clubbing.

J Dermatol 2019 Mar 27;46(3):e101-e102. Epub 2018 Aug 27.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

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http://dx.doi.org/10.1111/1346-8138.14614DOI Listing
March 2019

Complete type of pachydermoperiostosis with a novel mutation c.510G>A of the SLCO2A1 gene.

J Dermatol 2017 Dec 27;44(12):1411-1412. Epub 2016 Dec 27.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

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http://dx.doi.org/10.1111/1346-8138.13728DOI Listing
December 2017

Atopic dermatitis presenting as generalized poikiloderma with filaggrin gene mutation.

J Dermatol 2014 Mar 20;41(3):230-1. Epub 2013 Dec 20.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

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http://dx.doi.org/10.1111/1346-8138.12339DOI Listing
March 2014