The Role of Galectin-9 as Mediator of Atopic Dermatitis: Effect on Keratinocytes.

Mab P Corrêa,Solange C G P D'Ávila,Andréia M Leopoldino,Karin V Greco,Libnah L Areias,Rebeca D Correia-Silva,Cristiane D Gil

doi:10.3390/cells10040947

Abstract

Galectin-9 (Gal-9) is a beta-galactoside-binding protein with a variety of biological functions related to immune response. However, in allergic diseases, its mechanism of action is not fully understood. This study evaluates the expression pattern of Gal-9 in patients with atopic dermatitis (AD), in ovalbumin (OVA)-induced experimental atopic dermatitis (AD) in mice, as well as its effect on human keratinocytes. The skin of OVA-immunized BALB/c mice was challenged with drops containing OVA on days 11, 14–18, and 21–24. HaCaT cells were cultured in the following experimental conditions: control (growth medium only) or stimulated with TNF-α/IFN-γ, or IL-4, or IL-17 with or without Gal-9 treatment. AD was characterized by increased levels of Gal-9 in mouse and human skin, especially in the epidermis, and with a marked influx of Gal-9 positive eosinophils and mast cells compared to the control group. Gal-9 showed an immunomodulatory effect on keratinocytes by decreasing the release of IL-6 by IL-4-stimulated keratinocytes or increasing the IL-6 and RANTES levels by IL-17- or TNF-α/IFN-γ-stimulated cells, respectively. Under IL-17, Gal-9 treatment also altered the proliferation rate of cells. Overall, increased levels of Gal-9 in AD skin contribute to the control of inflammatory response and the proliferative process of keratinocytes, suggesting this lectin as a relevant therapeutic target.

Highlights

Atopic dermatitis (AD), known as atopic eczema, represents the most common inflammation of the skin, characterized by reddish lesions that itch, peel, and sometimes get wet
atopic dermatitis (AD) group, mast cells sh to the control groups group, severalseveral mast cells a weakersuggesting staining, suggesting greater cell activation with the consequent release show a weaker staining, greater cell activation with the consequent release of of me ators from cytoplasmic granules compared to the control condition (Figure mediators from cytoplasmic granules compared to the control condition (Figure 2c,d)
AD skin samples showed a significant increase in degranulated mast cells cells compared to controls, while the number of intact cells was similar between the d compared to controls, while the number of intact cells was similar between the different ferent experimental groups (Figure 2e,f)

Summary

Introduction

Atopic dermatitis (AD), known as atopic eczema, represents the most common inflammation of the skin, characterized by reddish lesions that itch, peel, and sometimes get wet. AD has an early onset and can affect 25% of children, with about 10% carrying the disease into adulthood [1,2]. AD patients have a higher incidence of bacterial, fungal, or viral infections due to epithelial barrier dysfunction in skin lesions. AD etiology is not completely clear, and it seems to be multifactorial as there is evidence that genetic predisposition and a family history of atopies can influence the onset of this disease. The barrier dysfunction occurs due to an impairment in keratinocytes’ terminal differentiation, which permits the penetration of antigens. Chronic pruritus and change in the pattern of resident microbiota support colonization by Staphylococcus aureus in the lesions [1,3]

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Discussion

Conclusion