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Protective role of Galectin‐7 for skin barrier impairment in atopic dermatitis
Author(s) -
Umayahara Takatsune,
Shimauchi Takatoshi,
Iwasaki Manami,
Sakabe Junichi,
Aoshima Masahiro,
Nakazawa Shinsuke,
Yatagai Tsuyoshi,
Yamaguchi Hayato,
Phadungsaksawasdi Pawit,
Kurihara Kazuo,
Tokura Yoshiki
Publication year - 2020
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.13672
Subject(s) - epidermis (zoology) , stratum corneum , gene knockdown , thymic stromal lymphopoietin , immunohistochemistry , filaggrin , atopic dermatitis , transepidermal water loss , stratum spinosum , keratinocyte , immunology , biology , microbiology and biotechnology , chemistry , pathology , in vitro , medicine , cell culture , anatomy , biochemistry , genetics
Abstract 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.