Development of allergen-induced airway inflammation in the absence of T-bet regulation is dependent on IL-17.
Development of allergen-induced airway inflammation in the absence of T-bet regulation is dependent on IL-17.
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DOI：
10.4049/jimmunol.0803109
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发表时间：
2009-10-15
期刊：
影响因子：
--
通讯作者：
Metzger DW
中科院分区：
文献类型：
--
作者：
Durrant DM;Gaffen SL;Riesenfeld EP;Irvin CG;Metzger DW
T-bet是一种对干扰素(IFN)-γ产生至关重要的转录因子，其功能失调表达与哮喘的发生有关。为了详细研究在T-bet表达缺失的情况下疾病加重的机制，BALB/c野生型（WT）和T-bet - / -小鼠被用于卵清蛋白（OVA）诱导的小鼠变应性肺部炎症模型。与WT小鼠相比，在OVA攻击后，T-bet - / -小鼠表现出肺部组织学炎症增加，细支气管内膜增厚，肺嗜酸性粒细胞和中性粒细胞数量增加，气道高反应性增强。然而，T-bet - / -小鼠中Th2细胞因子的产生似乎并不比WT小鼠显著增加。有趣的是，在T-bet - / -小鼠中观察到促炎细胞因子IL-17水平的显著增加。通过抗IL-17单抗治疗，T-bet - / -小鼠在OVA攻击期间肺IL-17被中和，导致气道中性粒细胞浸润水平下降，气道炎症减少，从根本上逆转过敏性哮喘的发展。这些发现表明，在T-bet缺失的情况下，IL-17是气道炎症的关键介质。本研究结果为人类哮喘的治疗干预提供了一个可能的靶点。
Dysfunctional expression of T-bet, a transcription factor that is critical for interferon (IFN)-γ production, has been implicated in the development of asthma. To investigate in detail the mechanisms responsible for exacerbated disease in the absence of T-bet expression, BALB/c wild-type (WT) and T-bet−/− mice were used in a murine model of ovalbumin (OVA)-induced allergic lung inflammation. Following OVA challenge, T-bet−/− mice displayed increased histological inflammation in the lungs as well as greater thickening of the bronchiole linings, increased numbers eosinophils and neutrophils in the lung, and enhanced airway hyperresponsiveness, compared to WT mice. However, the production of Th2 cytokines in T-bet−/− mice did not appear to be significantly greater than in WT mice. Interestingly, a marked increase in the levels of the pro-inflammatory cytokine IL-17 was observed in T-bet−/− mice. Neutralization of pulmonary IL-17 in T-bet−/− mice by anti-IL-17 mAb treatment during OVA challenge resulted in decreased levels of neutrophilic infiltration into the airways and decreased airway inflammation, essentially reversing the development of allergic asthma development. These findings indicate that IL-17 is a key mediator of airway inflammation in the absence of T-bet. The results of this study suggest a possible target for therapeutic intervention of human asthma.
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影响因子：
64.5
作者：
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通讯作者：
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DOI：
10.1164/ajrccm.154.5.8912732
发表时间：
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影响因子：
24.7
作者：
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通讯作者：
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