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首页> 外文期刊>Allergy >Thymic stromal lymphopoietin plays divergent roles in murine models of atopic and nonatopic airway inflammation
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Thymic stromal lymphopoietin plays divergent roles in murine models of atopic and nonatopic airway inflammation

机译：胸腺基质淋巴细胞生成素在特应性和非特应性气道炎症的小鼠模型中起不同作用

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Background: Thymic stromal lymphopoietin (TSLP) is a cytokine primarily produced by epithelial cells, which has been shown to be a potent inducer of T-helper 2 (Th2)-type responses. However, TSLP has pleiotropic effects upon immune cells, and although extensively studied in the context of atopic asthma, its relevance as a therapeutic target and its role in the pathogenesis of nonatopic asthma remains unknown. We sought to investigate the role of TSLP in atopic, nonatopic and viral-induced exacerbations of pulmonary inflammation.Methods: Using stringently defined murine models of atopic, nonatopic and virally exacerbated forms of pulmonary inflammation, we compared inflammatory responses of C57BL/6 wild-type (WT) and TSLP receptor-deficient (TSLPR KO) mice.Results: Thymic stromal lymphopoietin receptor (TSLPR) signaling was crucial for the development of atopic asthma. Specifically, TSLPR signaling to lung recruited CD4+ T cells enhanced eosinophilia, goblet cell hyperplasia, and overall inflammation within the airways. In contrast, the absence of TSLPR signaling was associated with strikingly exaggerated pulmonary neutrophilic inflammation in a nonatopic model of airway inflammation. The inflammation was associated with excessive levels of interleukin (IL)-17A in the lungs, indicating that TSLP negatively regulates IL-17A. In addition, in a model of influenza-induced exacerbation of atopic airway inflammation, the absence of TSLPR signaling also led to exaggerated neutrophilic inflammation.Conclusion: Thymic stromal lymphopoietin plays divergent roles in the pathogenesis of atopic and nonatopic asthma phenotypes by either enhancing Th2 responses or curtailing T-helper 17 responses. These findings raise important caveats for the design of therapeutic interventions targeting TSLP in asthma.
机译：背景：胸腺基质淋巴细胞生成素（TSLP）是主要由上皮细胞产生的细胞因子，已被证明是T辅助2（Th2）型反应的有效诱导剂。然而，TSLP对免疫细胞具有多效性作用，尽管在特应性哮喘的背景下进行了广泛研究，但其作为治疗靶标的相关性及其在非特应性哮喘发病中的作用仍然未知。我们试图研究TSLP在特应性，非特应性和病毒性肺炎加重中的作用。方法：使用严格定义的特应性，非特应性和病毒性肺炎加重的鼠模型，我们比较了C57BL / 6野生型小鼠的炎症反应结果：胸腺基质淋巴细胞生成素受体（TSLPR）信号对于特应性哮喘的发展至关重要。具体而言，向肺募集的CD4 + T细胞发送的TSLPR信号增强了嗜酸性粒细胞增多，杯状细胞增生和气道内的整体炎症。相反，在气道炎症的非特应性模型中，缺乏TSLPR信号传导与过度夸张的肺中性粒细胞炎症有关。炎症与肺中白介素（IL）-17A的过量水平相关，表明TSLP负调节IL-17A。此外，在流感诱导的特应性气道炎症加重模型中，缺乏TSLPR信号还导致夸大的中性粒细胞炎症。或减少T-helper 17的回应。这些发现为针对哮喘中TSLP的治疗性干预措施的设计提出了重要的警告。

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