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首页> 外文期刊>The Journal of Clinical Investigation: The Official Journal of the American Society for Clinical Investigation >Identification of an IFN-gamma/mast cell axis in a mouse model of chronic asthma.
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Identification of an IFN-gamma/mast cell axis in a mouse model of chronic asthma.

机译：在慢性哮喘小鼠模型中鉴定IFN-γ/肥大细胞轴。

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摘要

Asthma is considered a Th2 cell-associated disorder. Despite this, both the Th1 cell-associated cytokine IFN-gamma and airway neutrophilia have been implicated in severe asthma. To investigate the relative contributions of different immune system components to the pathogenesis of asthma, we previously developed a model that exhibits several features of severe asthma in humans, including airway neutrophilia and increased lung IFN-gamma. In the present studies, we tested the hypothesis that IFN-gamma regulates mast cell function in our model of chronic asthma. Engraftment of mast cell-deficient KitW(-sh/W-sh) mice, which develop markedly attenuated features of disease, with wild-type mast cells restored disease pathology in this model of chronic asthma. However, disease pathology was not fully restored by engraftment with either IFN-gamma receptor 1-null (Ifngr1-/-) or Fcepsilon receptor 1gamma-null (Fcer1g-/-) mast cells. Additional analysis, including gene array studies, showed that mast cell expression of IFN-gammaR contributed to the development of many FcepsilonRIgamma-dependent and some FcepsilonRIgamma-independent features of disease in our model, including airway hyperresponsiveness, neutrophilic and eosinophilic inflammation, airway remodeling, and lung expression of several cytokines, chemokines, and markers of an alternatively activated macrophage response. These findings identify a previously unsuspected IFN-gamma/mast cell axis in the pathology of chronic allergic inflammation of the airways in mice.
机译：哮喘被认为是一种Th2细胞相关疾病。尽管如此，Th1 细胞相关细胞因子 IFN-γ 和气道中性粒细胞增多都与严重哮喘有关。为了研究不同免疫系统成分对哮喘发病机制的相对贡献，我们之前开发了一个模型，该模型表现出人类严重哮喘的几个特征，包括气道中性粒细胞增多和肺IFN-γ增加。在本研究中，我们测试了IFN-γ在我们的慢性哮喘模型中调节肥大细胞功能的假设。在这种慢性哮喘模型中，肥大细胞缺陷的KitW（-sh/W-sh）小鼠的植入，其疾病特征明显减弱，野生型肥大细胞恢复了疾病病理学。然而，植入 IFN-γ 受体 1-null （Ifngr1-/-） 或 Fcepsilon 受体 1γ-null （Fcer1g-/-） 肥大细胞并不能完全恢复疾病病理学。包括基因阵列研究在内的其他分析表明，IFN-γR 的肥大细胞表达有助于我们模型中许多 FcepsilonRIgamma 依赖性和一些 FcepsilonRIgamma 非依赖性疾病特征的发展，包括气道高反应性、中性粒细胞和嗜酸性粒细胞炎症、气道重塑以及几种细胞因子、趋化因子和可变激活巨噬细胞反应标志物的肺表达。这些发现确定了小鼠气道慢性过敏性炎症病理学中以前未被怀疑的IFN-γ/肥大细胞轴。

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