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

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.

Activated Leukocyte Cell Adhesion Molecule Modulates Th2 Immune Response in Atopic Dermatitis.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Reduction Rate of Specific IgE Level as a Predictor of Persistent Egg Allergy in Children.

PURPOSE: Egg is the most common food allergen in infants. However, the natural course of egg allergy has not been fully elucidated. This study aimed to describe clinical characteristics and to identify prognostic factors associated with tolerance acquisition of immunoglobulin E (IgE)-mediated egg allergy in children. METHODS: Children who underwent more than 1 follow-up egg white-specific immunoglobulin E (EWsIgE) test between November 2005 and November 2015 at -Severance Children's Hospital were assessed. Children were diagnosed as having IgE-mediated egg allergy based on immediate allergic reaction after egg consumption and an EWsIgE level of > 0.35 kU/L. The children were divided into "tolerant" and "persistent" groups according to tolerance acquisition defined as egg consumption without adverse allergic reactions. RESULTS: Of 124 participants, egg allergy resolved in 101 (81.5%) children. The persistent group had more atopic dermatitis (P = 0.039), and more wheat (P = 0.009) and peanut (P = 0.012) allergies compared to the tolerant group. The EWsIgE levels at diagnosis (EWsIgEdiag) were higher in the persistent group than in the tolerant group (P = 0.001). The trend of the EWsIgE levels in the tolerant group decreased markedly over time compared to the persistent group (P < 0.001). In predicting egg allergy tolerance acquisition, the reduction rate of EWsIgE level after 12 months from diagnosis (ΔEWsIgE12mo) tended to be more accurate than EWsIgEdiag (area under the curve: 0.835 vs. 0.731). When ΔEWsIgE12mo was ≥ 30%, tolerance acquisition was more frequent than that of < 30% (91.9% vs. 57.9%; P < 0.001). CONCLUSIONS: ΔEWsIgE12mo can be used as an early independent predictor of tolerance acquisition of IgE-mediated egg allergy in children.