Intelectin contributes to allergen-induced IL-25, IL-33, and TSLP expression and type 2 response in asthma and atopic dermatitis.
Intelectin contributes to allergen-induced IL-25, IL-33, and TSLP expression and type 2 response in asthma and atopic dermatitis.
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Intelectin 有助于过敏原诱导的 IL-25、IL-33 和 TSLP 表达以及哮喘和特应性皮炎中的 2 型反应
DOI：
10.1038/mi.2017.10
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发表时间：
2017-11
影响因子：
8
通讯作者：
Zhen G
中科院分区：
文献类型：
--
作者：
Yi L;Cheng D;Zhang K;Huo X;Mo Y;Shi H;Di H;Zou Y;Zhang H;Zhao J;Xu Y;Erle DJ;Zhen G
上皮和表皮先天性细胞因子IL-25、IL-33和胸腺基质淋巴细胞生成素（TSLP）在哮喘和特应性皮炎的过敏性炎症的起始中起关键作用。然而，这些先天性细胞因子的表达调节的机制仍不清楚。在气道上皮细胞中表达并促进变应性气道炎症。我们假设ITLN是过敏原诱导的IL-25、IL-33和TSLP表达所必需的。在两种哮喘模型中，Itln敲低降低了过敏原诱导的IL-25、IL-33和Tslp的增加以及2型反应、嗜酸性粒细胞炎症、粘液过度产生和气道高反应性的发展。Itln敲低还抑制了在仅诱导气道致敏的模型中屋尘螨（HDM）诱导的IL-25、IL-33和Tslp的早期上调。使用人气道上皮细胞，我们证明了HDM诱导的ITLN增加导致EGFR和ERK磷酸化，这是诱导IL-25，IL-33和TSLP表达所必需的。在两种特应性皮炎模型中，Itln敲低抑制IL-33、Tslp和Th 2细胞因子的表达和嗜酸性粒细胞炎症。在人类中，ITLN 1的表达在哮喘气道和特应性皮炎皮损中显著增加。我们的结论是，intelectin有助于过敏原诱导的IL-25，IL-33和Tslp的表达在哮喘和特应性皮炎。
The epithelial and epidermal innate cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) play pivotal roles in the initiation of allergic inflammation in asthma and atopic dermatitis. However, the mechanism by which the expression of these innate cytokines is regulated remains unclear. Intelectin (ITLN) is expressed in airway epithelial cells and promotes allergic airway inflammation. We hypothesized that ITLN is required for allergen-induced IL-25, IL-33 and TSLP expression. In two asthma models, Itln knockdown reduced allergen-induced increases in Il-25, Il-33, and Tslp and development of type 2 response, eosinophilic inflammation, mucus overproduction, and airway hyperresponsiveness. Itln knockdown also inhibited house dust mite (HDM)-induced early upregulation of Il-25, Il-33, and Tslp in a model solely inducing airway sensitization. Using human airway epithelial cells, we demonstrated that HDM-induced increases in ITLN led to phosphorylation of EGFR and ERK which were required for induction of IL-25, IL-33, and TSLP expression. In two atopic dermatitis models, Itln knockdown suppressed expression of Il-33, Tslp and Th2 cytokines and eosinophilic inflammation. In humans, ITLN1 expression was significantly increased in asthmatic airways and in lesional skin of atopic dermatitis. We conclude that intelectin contributes to allergen-induced Il-25, Il-33 and Tslp expression in asthma and atopic dermatitis.
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影响因子：
3.7
作者：
Kotnik K;Popova E;Todiras M;Mori MA;Alenina N;Seibler J;Bader M
通讯作者：
Bader M
影响因子：
14.8
作者：
Hatzios SK;Abel S;Martell J;Hubbard T;Sasabe J;Munera D;Clark L;Bachovchin DA;Qadri F;Ryan ET;Davis BM;Weerapana E;Waldor MK
通讯作者：
Waldor MK
影响因子：
14.2
作者：
Corrigan, Chris J.;Wang, Wei;Ying, Sun
通讯作者：
Ying, Sun
DOI：
10.1073/pnas.1014241108
发表时间：
2011-01-25
影响因子：
11.1
作者：
Corrigan, Chris J.;Wang, Wei;Ying, Sun
通讯作者：
Ying, Sun
影响因子：
2.8
作者：
DaVeiga, Sigrid Payne
通讯作者：
DaVeiga, Sigrid Payne