IFN-γ acts on the airway epithelium to inhibit local and systemic pathology in allergic airway disease.

IFN-γ acts on the airway epithelium to inhibit local and systemic pathology in allergic airway disease.
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DOI:
10.4049/jimmunol.1100436
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发表时间:
2011-10-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Cohn L
Cohn L
中科院分区:
其他
文献类型:
--
作者:
Mitchell C;Provost K;Niu N;Homer R;Cohn L

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抑制过敏性呼吸道炎症是持续性哮喘治疗的目标。通过呼吸道给药直接将药物输送到炎症部位,避免全身副作用,但往往无法调节哮喘的全身特征。我们已经证明,Th1细胞通过产生干扰素-γ,抑制Th2诱导的许多促进疾病的效应功能。利用一只仅在呼吸道上皮细胞上表达干扰素-γR的新生小鼠,我们证明了呼吸道上皮控制哮喘的一系列病理反应。干扰素-γ只通过呼吸道上皮抑制粘液、几丁质酶和嗜酸性粒细胞,而不依赖Th2细胞的激活。通过呼吸道上皮细胞的干扰素-γ信号抑制骨髓中嗜酸性粒细胞的产生,表明呼吸道粘膜表面的信号可以调节远处的功能,从而抑制疾病。干扰素-γ通过呼吸道上皮发挥作用,可限制呼吸道阻塞和炎症,可能对难治性哮喘有治疗作用。
Inhibiting allergic airway inflammation is the goal of therapy in persistent asthma. Administration of medication via the airways delivers drug directly to the site of inflammation and avoids systemic side effects, but often fails to modulate systemic features of asthma. We have shown that Th1 cells, through production of IFN-γ, inhibit many Th2-induced effector functions that promote disease. Using a newly generated mouse that expresses IFN-γR only on airway epithelial cells, we show that the airway epithelium controls a range of pathological responses in asthma. IFN-γ acting only through the airway epithelium inhibits mucus, chitinases and eosinophilia, independent of Th2 cell activation. IFN-γ signaling through the airway epithelium inhibits eosinophil generation in the bone marrow, indicating that signals on the airway mucosal surface can regulate distant functions to inhibit disease. IFN-γ actions through the airway epithelium will limit airway obstruction and inflammation and may be therapeutic in refractory asthma.
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