Chitotriosidase inhibits allergic asthmatic airways via regulation of TGF-β expression and Foxp3(+) Treg cells.
Chitotriosidase inhibits allergic asthmatic airways via regulation of TGF-β expression and Foxp3(+) Treg cells.
复制标题
壳三醇苷酶通过调节TGF-β表达和Foxp3(+) Treg细胞抑制过敏性哮喘气道。
作者：
Hong JY;Kim M;Sol IS;Kim KW;Lee CM;Elias JA;Sohn MH;Lee CG
几丁三糖苷酶（Chitnase 1，Chit1）是人类中一种主要的真正几丁质酶，在儿童哮喘中被诱导，并且与多种炎症和组织重塑反应的发病机制有关。我们假设 Chit1 在过敏性哮喘的发病机制中发挥重要作用。为了确定 Chit1 的作用、这些贡献背后的机制以及这些小鼠研究结果与儿童哮喘的相关性。使用野生型和 Chit1 缺陷型小鼠以及培养细胞来确定 Chit1 在过敏性适应性 Th2 炎症模型中的作用。此外，还评估了儿童哮喘患者的痰液 Chit1 水平，并与对照组进行了比较。儿童哮喘患者痰液Chit1水平显着升高。 Chit1 缺失突变的小鼠表现出对 OVA 或屋尘螨过敏原致敏和攻击的过敏性 Th2 炎症、细胞因子和 IgE 反应增强。然而，与 WT 对照相比，Chit1−/− 小鼠肺部的 TGF-β1 表达水平随着 Foxp3+ 调节性 T 细胞 (Treg) 数量的减少而显着降低。在体外，Chit1 的缺失显着降低了 TGF-β 刺激的 CD4+CD25- 初始 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。
Chitotriosidase (Chitnase 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. We hypothesized that Chit1 plays a significant role in the pathogenesis of allergic asthma. To identify the role of Chit1, the mechanisms that underlie these contributions and the relevance of these murine findings to childhood 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.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
4.4
作者：
Da Silva, Carla A.;Chalouni, Cecile;Elias, Jack A.
通讯作者：
Elias, Jack A.
影响因子：
7
作者：
Lee, Chun Geun;Da Silva, Carla A.;Lee, Jae-Young;Hartl, Dominik;Elias, Jack A.
通讯作者：
Elias, Jack A.
DOI：
10.1084/jem.20081271
发表时间：
2009-05-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lee CG;Hartl D;Lee GR;Koller B;Matsuura H;Da Silva CA;Sohn MH;Cohn L;Homer RJ;Kozhich AA;Humbles A;Kearley J;Coyle A;Chupp G;Reed J;Flavell RA;Elias JA
通讯作者：
Elias JA
影响因子：
30.5
作者：
Dardalhon, Valerie;Awasthi, Amit;Kwon, Hyoung;Galileos, George;Gao, Wenda;Sobel, Raymond A.;Mitsdoerffer, Meike;Strom, Terry B.;Elyaman, Wassim;Ho, I-Cheng;Khoury, Samia;Oukka, Mohamed;Kuchroo, Vijay K.
通讯作者：
Kuchroo, Vijay K.