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Clinical Trial
. 2019 Nov;49(11):1464-1474.
doi: 10.1111/cea.13478. Epub 2019 Aug 28.

Chitinase 3-like 1 drives allergic skin inflammation via Th2 immunity and M2 macrophage activation

Eun Ji Kwak  1 , Jung Yeon Hong  1 , Mi Na Kim  1 , Soo Yeon Kim  1 , Seo Hyeong Kim  2 , Chang Ook Park  2 , Kyung Won Kim  1 , Chun Geun Lee  3   4 , Jack A Elias  3 , Hye Mi Jee  5 , Myung Hyun Sohn  1
Affiliations
Clinical Trial

Chitinase 3-like 1 drives allergic skin inflammation via Th2 immunity and M2 macrophage activation

Eun Ji Kwak et al. Clin Exp Allergy. 2019 Nov.

Abstract

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.

Keywords: atopic dermatitis; chitinase 3-like 1; skin barrier; type 2 immunity.

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References

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