Cystic fibrosis: a mucosal immunodeficiency syndrome.
Cystic fibrosis: a mucosal immunodeficiency syndrome.
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囊性纤维化跨膜传导调节因子（CFTR）作为一种通道，调节离子的转运和水穿过上皮屏障的运动。CFTR的突变形成囊性纤维化临床表现的基础，影响肺中的上皮先天免疫功能，导致无法根除肺部病原体的过度和无效的气道炎症。复合过度中性粒细胞募集的作用，突变CFTR通道不运输抗氧化剂来抵消嗜中性粒细胞相关的氧化应激。尽管突变CFTR在肺外白细胞中的表达不会显著损害其功能，但在囊性纤维化中，气道中炎症的预期调节明显不足。由此产生的细菌感染，这是由具有相当大的遗传和代谢灵活性的生物体引起的，可以抵抗多种抗生素并逃避吞噬细胞清除。开发接近人类肺部表型-气道炎症和自发性感染-的动物模型可能提供急需的工具，以确定CFTR如何调节粘膜免疫，并直接测试药理学增强和校正突变CFTR功能对细菌清除的影响。
Cystic fibrosis transmembrane conductance regulator (CFTR) functions as a channel that regulates the transport of ions and the movement of water across the epithelial barrier. Mutations in CFTR, which form the basis for the clinical manifestations of cystic fibrosis, affect the epithelial innate immune function in the lung, resulting in exaggerated and ineffective airway inflammation that fails to eradicate pulmonary pathogens. Compounding the effects of excessive neutrophil recruitment, the mutant CFTR channel does not transport antioxidants to counteract neutrophil-associated oxidative stress. Whereas mutant CFTR expression in leukocytes outside of the lung does not markedly impair their function, the expected regulation of inflammation in the airways is clearly deficient in cystic fibrosis. The resulting bacterial infections, which are caused by organisms that have substantial genetic and metabolic flexibility, can resist multiple classes of antibiotics and evade phagocytic clearance. The development of animal models that approximate the human pulmonary phenotypes—airway inflammation and spontaneous infection—may provide the much-needed tools to establish how CFTR regulates mucosal immunity and to test directly the effect of pharmacologic potentiation and correction of mutant CFTR function on bacterial clearance.
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DOI：
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