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.

Kim EG, et al. Allergy Asthma Immunol Res. 2020 Nov;12(6):1012-1028. https://doi.org/10.4168/aair.2020.12.6.1012

Background: Chitotriosidase (chitinase 1, Chit1), a major true chitinase in humans, is induced in childhood asthma and has been implicated in the pathogenesis of a variety of inflammatory and tissue remodeling responses. However, the role and the mechanisms that underlie these contributions to the diseases have not been defined. We hypothesized that Chit1 plays a significant role in the pathogenesis of allergic asthma.Methods: Wild‐type and Chit1‐deficient mice and cells in culture were used to define the roles of Chit1 in models of allergic adaptive Th2 inflammation. In addition, the levels of sputum Chit1 were evaluated in pediatric asthma patients and compared to control.Results: The levels of sputum Chit1 were significantly increased in the patients with childhood asthma. Mice with Chit1 null mutation demonstrated enhanced allergic Th2 inflammatory and cytokine and IgE responses to OVA or house dust mite allergen sensitization and challenge. However, the expression levels of TGF‐β1 were significantly decreased with a diminished number of Foxp3⁺ regulatory T cells (Treg) in the lungs of Chit1^−/− mice compared to WT controls. In vitro, the absence of Chit1 significantly reduced TGF‐β‐stimulated conversion of CD4⁺CD25⁻ naïve T cells to CD4⁺Foxp3⁺ Treg cells, suggesting Chit1 is required for optimal effect of TGF‐β1 in Treg cell differentiation.Conclusion: Chit1 plays a protective role in the pathogenesis of allergic inflammation and asthmatic airway responses via regulation of TGF‐β expression and Foxp3⁺ Treg cells.

Rationale: The activated leukocyte cell adhesion molecule (ALCAM) is a cluster of differentiation 6 ligand that is important for stabilizing the immunological synapse and inducing T-cell activation and proliferation. Objectives: In this study, we investigated the role of ALCAM in the development of inflammation in allergic asthma. Methods: An ovalbumin (OVA)-induced allergic asthma model was established in wild-type (WT) and ALCAM-deficient (ALCAM−/−) mice. T-cell proliferation was evaluated in cocultures with dendritic cells (DCs). Bone marrow–derived dendritic cells (BMDCs) from WT and ALCAM−/− mice were cultured and adoptively transferred to OT-II mice for either OVA sensitization or challenge. An anti-ALCAM antibody was administered to assess its therapeutic potential. ALCAM concentrations in the sputum and serum of children with asthma were quantified by ELISA. Measurements and Main Results: Inflammatory responses were lower in ALCAM−/− mice than in WT mice, and T cells cocultured with DCs from ALCAM−/− mice showed reduced proliferation relative to those cocultured with DCs from WT mice. A decreased inflammatory response was observed upon adoptive transfer of BMDCs from ALCAM−/− mice as compared with that observed after transfer of BMDCs from WT mice. In addition, anti-ALCAM antibody–treated mice showed a reduced inflammatory response, and sputum and serum ALCAM concentrations were higher in children with asthma than in control subjects. Conclusions: ALCAM contributes to OVA-induced allergic asthma by stimulating T-cell activation and proliferation, suggesting it as a potential therapeutic target for allergic asthma.