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

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.

Functions and Inhibition of Galectin-7, an Emerging Target in Cellular Pathophysiology

“…A galectin-7 knockdown experiment on a 3D-reconstructed epidermis was performed; it resulted that endogenous galectin-7 protects IL-4/IL-13–induced disruption of cell-to-cell adhesion and/or cell-to-extracellular matrix adhesion. In addition, IL-4/IL-13–induced galectin-7 release from keratinocytes reflects the skin barrier impairment in AD patients [ 87 ].…”

Diagnostic Tools and Biomarkers for Severe Drug Eruptions

“…Galectin-7 was identified as the possible proteins as a biomarker for SJS/TEN and the serum concentration of galectin-7 was increased in the 24 patients with SJS/TEN compared with that in 8 healthy subjects. The weakness of the galectin-7 is not a specific marker of drug eruption, and is also seen in other inflammatory skin diseases, such as atopic dermatitis [ 100 ] and UV radiation [ 101 ], while it is decreased in psoriasis [ 102 ].…”

“…Serum miR-18a-5p and miR-124 are increased in patients with severe cutaneous adverse events drug eruption, however, the timing of blood sample collection and specificity are not defined [ 33 , 34 ], and it remains unclear whether these are derived from tissue damage reaction or the possible pathogenesis. Galectin-7 concentration in serum increases in SJS/TEN patients before treatment, however, this is not a specific finding in drug eruption and is also upregulated in other inflammatory diseases as a result of tissue damage [ 100 ]. HMGB1 is constitutively increased in SJS/TEN and this significantly increases compared with other types of drug eruption and healthy subjects [ 62 , 63 ], which means an increase in the value of HMGB1 does not necessarily reflect the clinical time course point, however, HMGB1 is not a specific marker for drug eruptions [ 147 , 148 ].…”

Developments in the field of allergy in 2020 through the eyes of Clinical and Experimental Allergy

“…Papers in the journal last year evaluated possible relationships with vitamin A deficiency, with Caesarean delivery and a possible association with alopecia areata, suggesting potential common genetic or immune pathways 100‐102 . Others evaluated machine learning, neuronal/immune interactions, fungal sensitization and skin barrier in eczema 103‐106 …”