Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Molecular Microbiology and Immunology, Brown University, Providence, RI, USA.
Allergy. 2018 Aug;73(8):1686-1699. doi: 10.1111/all.13426. Epub 2018 Mar 5.
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.
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.
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.
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.
几丁质酶 1（Chit1），人类中主要的真正几丁质酶，在儿童哮喘中被诱导产生，并与多种炎症和组织重塑反应的发病机制有关。然而，这些对疾病的贡献的作用和机制尚未确定。我们假设 Chit1 在过敏性哮喘的发病机制中起重要作用。
使用野生型和 Chit1 缺陷型小鼠以及培养细胞来定义 Chit1 在过敏性适应性 Th2 炎症模型中的作用。此外，评估了儿科哮喘患者的痰液 Chit1 水平，并与对照组进行了比较。
儿童哮喘患者的痰液 Chit1 水平显著升高。Chit1 缺失突变的小鼠对 OVA 或屋尘螨变应原致敏和激发表现出增强的过敏性 Th2 炎症和细胞因子及 IgE 反应。然而，与 WT 对照相比，Chit1 小鼠肺中的 TGF-β1 表达水平显著降低，Foxp3 调节性 T 细胞（Treg）的数量减少。体外，缺乏 Chit1 显著降低了 TGF-β 刺激的 CD4 CD25 幼稚 T 细胞向 CD4 Foxp3 Treg 细胞的转化，表明 Chit1 是 TGF-β1 在 Treg 细胞分化中发挥最佳作用所必需的。
Chit1 通过调节 TGF-β表达和 Foxp3 Treg 细胞在过敏性炎症和哮喘气道反应的发病机制中发挥保护作用。
