内凝集素促进了过敏原诱导的IL-25、IL-33、TSLP表达及哮喘、特异性皮炎中的2型过敏反应
2017/11/20
摘要
上皮和表皮的固有细胞因子IL-25、IL-33、胸腺基质淋巴细胞生成素（TSLP）在哮喘和特异性皮炎（AD）急性过敏炎症发生中起到了关键作用。然而，调控这些固有细胞因子表达的机制尚不清楚。内凝集素（ITLN）在气道上皮中表达，促进了气道变应性炎症。我们猜想，ITLN与过敏原诱导的IL-25、IL-33、TSLP表达有关。在两种哮喘模型中，ITLN敲除后过敏原诱导的IL-25、IL-33、TSLP表达减少，2型反应、嗜酸性粒细胞炎症、黏液高分泌、气道高反应性减弱。在单纯气道致敏的模型中，ITLN还抑制了室内尘螨（HDM）诱导的IL-25、IL-33、TSLP的早期上调。我们在人气道上皮中证明，HDM诱导ITLN增加导致了表皮生长因子受体和细胞外信号调节激酶的磷酸化，从而诱导了IL-25、IL-33和TSLP的表达。在两种AD模型中，ITLN敲除抑制了IL-33、TSLP、Th2细胞因子表达和嗜酸性粒细胞炎症。在人哮喘的气道及AD皮损处ITLN1表达显著增加。我们推断在哮喘和AD中，ITLN促进了过敏原诱导的IL-25、IL-33和TSLP的表达。
Intelectin contributes to allergen-induced IL-25, IL-33, and TSLP expression and type 2 response in asthma and atopic dermatitis.
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.
Abstract
The epithelial and epidermal innate cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) have pivotal roles in the initiation of allergic inflammation in asthma and atopic dermatitis (AD). 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 epidermal growth factor receptor and extracellular-signal regulated kinase, which were required for induction of IL-25, IL-33, and TSLP expression. In two AD 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 AD. We conclude that ITLN contributes to allergen-induced Il-25, Il-33, and Tslp expression in asthma and AD.
上皮和表皮的固有细胞因子IL-25、IL-33、胸腺基质淋巴细胞生成素（TSLP）在哮喘和特异性皮炎（AD）急性过敏炎症发生中起到了关键作用。然而，调控这些固有细胞因子表达的机制尚不清楚。内凝集素（ITLN）在气道上皮中表达，促进了气道变应性炎症。我们猜想，ITLN与过敏原诱导的IL-25、IL-33、TSLP表达有关。在两种哮喘模型中，ITLN敲除后过敏原诱导的IL-25、IL-33、TSLP表达减少，2型反应、嗜酸性粒细胞炎症、黏液高分泌、气道高反应性减弱。在单纯气道致敏的模型中，ITLN还抑制了室内尘螨（HDM）诱导的IL-25、IL-33、TSLP的早期上调。我们在人气道上皮中证明，HDM诱导ITLN增加导致了表皮生长因子受体和细胞外信号调节激酶的磷酸化，从而诱导了IL-25、IL-33和TSLP的表达。在两种AD模型中，ITLN敲除抑制了IL-33、TSLP、Th2细胞因子表达和嗜酸性粒细胞炎症。在人哮喘的气道及AD皮损处ITLN1表达显著增加。我们推断在哮喘和AD中，ITLN促进了过敏原诱导的IL-25、IL-33和TSLP的表达。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Mucosal Immunol. 2017 Nov; 10(6):1491-1503.)
(Mucosal Immunol. 2017 Nov; 10(6):1491-1503.)
Intelectin contributes to allergen-induced IL-25, IL-33, and TSLP expression and type 2 response in asthma and atopic dermatitis.
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.
Abstract
The epithelial and epidermal innate cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) have pivotal roles in the initiation of allergic inflammation in asthma and atopic dermatitis (AD). 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 epidermal growth factor receptor and extracellular-signal regulated kinase, which were required for induction of IL-25, IL-33, and TSLP expression. In two AD 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 AD. We conclude that ITLN contributes to allergen-induced Il-25, Il-33, and Tslp expression in asthma and AD.
