Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology
Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology
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DOI：
10.1172/jci200213696
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发表时间：
2002-01-01
影响因子：
15.9
通讯作者：
Flavell, RA
中科院分区：
文献类型：
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作者：
Temann, UA;Ray, P;Flavell, RA
IL-9是一种多效性细胞因子，在参与人类哮喘病理学的许多细胞类型上具有多种功能。转基因小鼠肺中IL-9的组成性过表达导致哮喘样表型。为了确定IL-9对肺部炎症的贡献，我们产生了转基因小鼠，其中IL-9转基因的肺特异性表达是由多西环素诱导的。转基因诱导导致肺的淋巴细胞和嗜酸性粒细胞浸润、气道上皮细胞肥大伴粘液产生和肥大细胞增生，与在肺中组成性表达IL-9的小鼠中观察到的相似。各种细胞因子，包括IL-4、IL-5和IL-13，在肺中响应于IL-9而表达。在IL-9诱导后阻断IL-4或IL-5可减少气道嗜酸性粒细胞增多而不影响粘液产生。相反，IL-13的中和完全消除了肺部炎症和粘液产生。这些发现表明，肺中的病理变化需要由IL-4、IL-5和IL-13提供的IL-9以外的额外信号才能充分发展。
IL-9 is a pleiotropic cytokine with multiple functions on many cell types involved in the pathology of human asthma. The constitutive overexpression of IL-9 in the lungs of transgenic mice resulted in an asthma-like phenotype. To define the contribution of IL-9 to lung inflammation we generated transgenic mice in which lung-specific expression of the IL-9 transgene is inducible by doxycycline. Transgene induction resulted in lymphocytic and eosinophilic infiltration of the lung, airway epithelial cell hypertrophy with mucus production, and mast cell hyperplasia, similar to that seen in mice that constitutively expressed IL-9 in their lungs. Various cytokines, including IL-4, IL-5, and IL-13, were expressed in the lung in response to IL-9. Blockade of IL-4 or IL-5 following IL-9 induction reduced airway eosinophilia without affecting mucus production. In contrast, neutralization of IL-13 completely abolished both lung inflammation and mucus production. These findings suggest that pathologic changes in the lung require additional signals beyond IL-9, provided by IL-4, IL-5, and IL-13, to develop fully.