Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation
Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation
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DOI：
10.1002/eji.200939724
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发表时间：
2010-03
影响因子：
5.4
通讯作者：
M. Torii;Linan N. Wang;Ning Ma;Kanako Saito;T. Hori;M. Sato-Ueshima;Y. Koyama;H. Nishikawa;N. Katayama;A. Mizoguchi;H. Shiku;J. Yodoi;K. Kuribayashi;Takuma Kato
中科院分区：
文献类型：
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作者：
M. Torii;Linan N. Wang;Ning Ma;Kanako Saito;T. Hori;M. Sato-Ueshima;Y. Koyama;H. Nishikawa;N. Katayama;A. Mizoguchi;H. Shiku;J. Yodoi;K. Kuribayashi;Takuma Kato
氧化应激通过上调局部炎症介质和/或促进Ag致敏过程中的Th 2-偏移在哮喘发病机制中起重要作用。硫氧还蛋白（TRX）是一种具有抗氧化特性的12 kDa氧化还原活性蛋白，最近已被证明在各种炎症性疾病中发挥保护作用。使用哮喘小鼠模型，我们在这里显示TRX-Tg小鼠中IL-13和嗜酸性粒细胞活化趋化因子的产生减少，导致嗜酸性粒细胞募集和粘液化生减少。气道炎症的减轻在没有全身性Th 2免疫减弱的情况下发生，因为在TRX-Tg和WT小鼠的LN和血清中分别检测到相当水平的Th 2型细胞因子和IG。同样，来自两种小鼠品系的CD 4 + T细胞在体外产生了相似的Th 1和Th 2应答。TRX-Tg和WT小鼠的哮喘肺含有相似量的加塔-3+和Foxp 3 + T细胞。最后，TRX-Tg小鼠肺部的MIF（气道炎症上游调节剂）的产生显着减少。我们的数据表明，TRX抑制气道炎症，通过抑制MIF的生产，从而限制下游招募嗜酸性粒细胞的肺独立的调节系统性Th 1/Th 2免疫。
Oxidative stress plays an important role in the pathogenesis of asthma via the upregulation of local inflammatory mediators and/or promoting Th2‐skewing during Ag sensitization. Thioredoxin (TRX), a 12 kDa redox‐active protein with antioxidative property, has been recently shown to play a protective role in various inflammatory diseases. Using a mouse model of asthma, we show here that IL‐13 and eotaxin production are decreased in TRX‐Tg mice leading to reduced eosinophils recruitment and mucus metaplasia. The reduction in airway inflammation occurs without the attenuation of systemic Th2 immunity in that comparable levels of Th2‐type cytokines and Ig were detected in LN and serum, respectively, from TRX‐Tg and WT mice. Likewise, CD4+ T cells from both strains of mice developed similar Th1 and Th2 responses in vitro. Asthmatic lungs of TRX‐Tg and WT mice contained similar amounts of GATA‐3+ and Foxp3+ T cells. Finally, production of MIF, an upstream modulator of airway inflammation, was significantly reduced in the lungs of TRX‐Tg mice. Our data suggest that TRX suppresses airway inflammation by inhibiting MIF production thereby limiting the downstream recruitment of eosinophils to the lung independently of modulating systemic Th1/Th2 immunity.