The present study investigated the relationship between serum thymic stromal lymphopoietin (TSLP) levels and the presence and severity of atopic dermatitis (AD). Serum TSLP levels, blood eosinophil counts, and serum total and specific immunoglobulin E (IgE) levels were measured in 232 children. Subjects were characterized as having atopic eczema (AE; n=75), non-atopic eczema (NAE; n=70), or normal controls (n=87). Serum TSLP levels in children with AD were significantly higher than normal controls but there were no differences in children with atopic and non-atopic eczema. However, serum TSLP levels in children with AD were not significantly correlated with disease severity, blood eosinophil counts and serum total IgE levels. Our findings show an association between TSLP and AD including both AE and NAE. It is suggested that TSLP may play a contributory role in the pathogenesis of AD regardless of the presence of atopy.
Background
Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by defective skin barrier and Th2 immune responses. Chitinase 3‐like 1 (CHI3L1), also known as breast regression protein 39 (BRP‐39) in mice and human homologue YKL‐40, plays important roles in Th2 inflammation and allergen sensitization. CHI3L1 has been implicated in a variety of diseases including asthma characterized by inflammation, apoptosis and tissue remodelling, but its role in AD remains elusive.
Objective
The aim of this study was to investigate the role of CHI3L1 in the development and progression of AD.
Results
We investigated YKL‐40 levels in the serum and skin of AD patients by ELISA and immunofluorescence, respectively. Using a murine model of AD induced by ovalbumin (OVA), we investigated Th2 immune responses, M2 macrophage activation and skin barrier gene expression using wild‐type (WT) and BRP‐39 null mutant (BRP‐39−/−) mice.
YKL‐40 level was significantly increased in serum of AD patients. In addition, both mRNA and protein expression levels of BRP‐39 were higher in OVA‐sensitized WT mice than in control mice. OVA‐sensitized BRP‐39−/− mice showed decreased epidermal thickness, lower total serum IgE, Th2 cytokine levels and CD4+ effector T cell populations than OVA‐sensitized WT mice. Induction of BRP‐39 was dominant in dermal macrophages. BRP‐39 deficiency was found to be involved in M2 macrophage activation. Consistently, the YKL‐40 level in the skin of AD patients was higher than in normal subjects and it was expressed in dermal macrophages. BRP‐39 deficiency attenuated dysregulation of skin barrier and tight junction genes.
Conclusions and Clinical Relevance
These findings demonstrate that CHI3L1 mediates the development of AD induced by OVA, affecting Th2 inflammation, M2 macrophage activation and skin barrier function.
ALCAM contributes to OVA-induced allergic asthma by stimulating T-cell activation and proliferation, suggesting it as a potential therapeutic target for allergic asthma.
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