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Key regulators of sensitization and tolerance: GM-CSF, IL-10, TGF-β and the Notch signaling pathway in adjuvant-free experimental models of respiratory allergy.
International Reviews of Immunology ( IF 4.3 ) Pub Date : 2013-06-19 , DOI: 10.3109/08830185.2013.794457
George V Guibas 1 , Michael Makris , Nikolaos G Papadopoulos
Affiliation  

Conventional experimental models of respiratory allergy have contributed greatly to our current knowledge of the pathophysiology of allergic airway diseases; nevertheless, they are contingent upon unnatural sensitization techniques, entailing adjuvant-aided intraperitoneal (i.p) administration of antigen. Currently, there is a growing appreciation of the impact of tolerance mechanics in the pathophysiology of respiratory allergy. Thus, inasmuch as adjuvants exert a robust tolerance-modifying action, a transition from the conventional method of experimental sensitization to one that is more naturally and clinically relevant becomes important. We therefore opted to survey the literature and identify agents that could interfere with sensitization mechanics following non-adjuvant-aided airway exposure of laboratory rodents to aeroallergen. GM-CSF was found to exert robust Th2-polarizing action in this setting. Conversely, IL-10 fulfilled an important, albeit not so clear-cut, tolerance-favoring role; TGF-β was also identified as a likely instigator of tolerogenesis. The role of Notch signaling in the sensitization versus tolerance dilemma appeared to be important but diverse. Collectively, these factors appeared to profoundly and diversely modulate the balance between tolerance and sensitization in naturally relevant experimental models of allergic airway disease.

中文翻译:

在无佐剂的呼吸道过敏性实验模型中,敏化和耐受性的关键调节因子:GM-CSF,IL-10,TGF-β和Notch信号通路。

常规的呼吸道过敏实验模型为我们目前对过敏性气道疾病的病理生理学知识做出了巨大贡献。但是,它们取决于非自然的致敏技术,需要佐剂辅助腹膜内(ip)施用抗原。当前,对耐受机制在呼吸道过敏的病理生理学中的影响的认识日益增加。因此,由于佐剂发挥了强大的耐受性改变作用,从常规的实验致敏方法向更自然和临床相关的方法的转变变得重要。因此,我们选择对文献进行调查,并确定在实验室用啮齿动物非佐剂辅助气道暴露于气变应原后可能会干扰致敏机制的物质。发现在这种情况下,GM-CSF具有强大的Th2极化作用。相反,IL-10发挥了重要作用,尽管作用不那么明确,但对耐受性有帮助。TGF-β也被确定为可能的耐受性诱因。Notch信号在敏化性和耐受性困境中的作用似乎很重要,但却是多种多样的。总的来说,在自然相关的过敏性气道疾病实验模型中,这些因素似乎深刻而多样地调节了耐受性和致敏性之间的平衡。Notch信号在敏化性和耐受性困境中的作用似乎很重要,但却是多种多样的。总的来说,在自然相关的过敏性气道疾病实验模型中,这些因素似乎深刻而多样地调节了耐受性和致敏性之间的平衡。Notch信号在敏化性和耐受性困境中的作用似乎很重要,但却是多种多样的。总的来说,在自然相关的过敏性气道疾病实验模型中,这些因素似乎深刻而多样地调节了耐受性和致敏性之间的平衡。
更新日期:2019-11-01
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