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.

Samra MS, et al. Allergy Asthma Immunol Res. 2021 Jan;13(1):56-74. https://doi.org/10.4168/aair.2021.13.1.56

Lee HY, et al. Allergy Asthma Immunol Res. 2023 Nov;15(6):725-756. https://doi.org/10.4168/aair.2023.15.6.725

Ha EK, et al. J Korean Med Sci. 2022 Feb;37(8):e63. https://doi.org/10.3346/jkms.2022.37.e63

YKL-40, also known as chitinase-3-like protein 1, is an inflammatory glycoprotein that is secreted by various cell types under acute, chronic, and subclinical inflammation conditions. Elevated serum YKL-40 levels are reportedly independently related to diabetes mellitus, coronary artery disease, acute myocardial infarction, and cardiovascular mortality in adults. Therefore, we aimed to investigate the relationship between serum YKL-40 levels, lipid abnormalities, and the atherogenic index of plasma (AIP) in children. We enrolled 479 children aged 10–12 years (mean age: 11.52) in this general population-based, cross-sectional study. All subjects completed questionnaires and were subjected to multifrequency bioelectrical impedance analysis (BIA) to measure their height, weight, and body mass index (BMI). We collected serum samples from all participants to measure YKL-40, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels. Mean serum YKL-40 levels were significantly higher in the low-HDL-C ( ) and high-TG ( ) groups but were not related to TC and LDL-C levels. YKL-40 levels were also higher in the high AIP group ( ). After adjusting for age, gender, and BMI -score, the associations between serum YKL-40 levels and TG levels ( ), the TG-to-HDL-C ratio ( ), and the AIP value ( ) remained significant. Based on these findings, we suggest that serum YKL-40 may be a useful initial screening tool or follow-up risk indicator for lipid abnormalities, atherosclerosis, and cardiovascular disease in children and adolescents with risk factors, regardless of obesity.

Activated leukocyte cell adhesion molecule (ALCAM), a member of the immunoglobulin superfamily, is highly expressed on dendritic cells. ALCAM and its receptor CD6 are co-stimulatory molecules in the immunological synapse; their interaction is required for T cell activation. While atopic dermatitis (AD) is recognized as a T helper 2 (Th2)-mediated allergic disease, the role of ALCAM in its pathogenesis is unclear. ALCAM levels were measured in the serum of AD patients and AD-induced murine model by ovalbumin treatment. We next investigated transepidermal water loss, clinical score, Th2-immune responses, skin barrier gene expression and T-cell activation using wild-type (WT) and ALCAM deficiency mice. An oxazolone-induced AD-like model was also established and analyzed using WT- and ALCAM-deficient mice. We found that serum ALCAM levels were elevated in pediatric AD patients as well as WT AD mice, whereas Th2-type cytokine production and AD symptoms were suppressed in ALCAM-deficient mice. In addition, CD4⁺ effector T-cell counts in murine skin and skin-draining lymph nodes were lower in ALCAM-deficient mice than in their WT counterparts. ALCAM deficiency was also linked to higher expression of skin barrier genes and number of lamellar bodies. These findings indicate that ALCAM may contribute to AD pathogenesis by meditating a Th2-dominant immune response and disrupting the barrier function of the skin.