Trichosanthin functions as Th2-type adjuvant in induction of allergic airway inflammation

Trichosanthin functions as Th2-type adjuvant in induction of allergic airway inflammation
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天花粉素作为 Th2 型佐剂诱导过敏性气道炎症

DOI:
10.1038/cr.2009.77
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发表时间:
2009-08
期刊:
影响因子:
44.1
通讯作者:
Wang, Yuan
Wang, Yuan
中科院分区:
生物学1区
文献类型:
--
作者:
Mao, Kairui;Sun, Bing;Sun, Shuhui;Lin, Guomei;Wu, Xiaodong;Yao, Gang;Wang, Yuan

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了解天然变应原诱发哮喘的发病机制,对于排除人工佐剂的干扰,了解疾病中的天然免疫应答具有重要意义。在本研究中,我们发现天花粉蛋白(TCS)可以诱导气道炎症,即使没有明矾的帮助。此外,TCS似乎能够取代明矾,以促进OVA特异性气道炎症。TCS在早期诱导产生IL-4的嗜酸性粒细胞在腹膜中积聚,并且TCS的佐剂作用在此阶段通过阻断IL-4而被消除。最后,由来自WT小鼠的TCS而不是来自IL-4缺陷小鼠的TCS触发的嗜酸性粒细胞显示出作为诱导OVA特异性Th 2应答的佐剂的功能。我们的数据表明,TCS不仅是一种过敏原,而且是一种Th 2型佐剂,调节免疫应答向Th 2途径的转换。这一系列事件是由于在TCS引发的早期阶段嗜酸性粒细胞产生IL-4所致。总之,TCS可用作Th 2佐剂,并且先天性免疫细胞,如嗜酸性粒细胞,可为研究Th 2应答起始的良好靶标。
It is important to understand the pathogenesis of asthma induced by natural allergens, which could exclude the interference of artificial adjuvant and provide insights of natural immune response in the disease. In the present study, we show that Trichosanthin (TCS) could induce airway inflammation even without the help of alum. Furthermore, TCS appeared capable of replacing alum to promote OVA-specific airway inflammation. TCS induced accumulation of IL-4-producing eosinophils in peritoneum at an early stage and the adjuvant function of TCS was eliminated by blockage of IL-4 at this stage. Finally, the eosinophils triggered by TCS from WT mice, but not from IL-4-deficient mice were shown to function as adjuvant for the induction of OVA-specific Th2 responses. Our data indicate that TCS is not only an allergen, but also a Th2-type adjuvant modulating the switching of immune responses to a Th2 pathway. This chain of events results from IL-4 production by eosinophils at an early stage of TCS-priming. In conclusion, TCS may be useful as a Th2 adjuvant, and innate immune cells, such as eosinophils, may be a good target to study the initiation of Th2 response.
由 Toll 样受体复合蛋白的功能模拟引起的过敏性。
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