Cystic fibrosis (CF) is one of the most common life-limiting recessive genetic disorders in Caucasians, caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CF is a multi-organ disease that involves the lungs, pancreas, sweat glands, digestive and reproductive systems and several other tissues. This debilitating condition is associated with recurrent lower respiratory tract bacterial and viral infections, as well as inflammatory complications that may eventually lead to pulmonary failure. Immune cells play a crucial role in protecting the organs against opportunistic infections and also in the regulation of tissue homeostasis. Innate immune cells are generally affected by CFTR mutations in patients with CF, leading to dysregulation of several cellular signalling pathways that are in continuous use by these cells to elicit a proper immune response. There is substantial evidence to show that airway epithelial cells, neutrophils, monocytes and macrophages all contribute to the pathogenesis of CF, underlying the importance of the CFTR in innate immune responses. The goal of this review is to put into context the important role of the CFTR in different innate immune cells and how CFTR dysfunction contributes to the pathogenesis of CF, highlighting several signalling pathways that may be dysregulated in cells with CFTR mutations.

中文翻译：

---

具有囊性纤维化突变的先天免疫细胞中信号通路失调。


囊性纤维化（CF）是白种人中最常见的限制生命的隐性遗传性疾病之一，由囊性纤维化跨膜电导调节因子（CFTR）突变引起。 CF是一种多器官疾病，涉及肺、胰腺、汗腺、消化系统和生殖系统以及其他几个组织。这种使人衰弱的病症与反复下呼吸道细菌和病毒感染以及最终可能导致肺衰竭的炎症并发症有关。免疫细胞在保护器官免受机会性感染以及调节组织稳态方面发挥着至关重要的作用。先天免疫细胞通常会受到 CF 患者 CFTR 突变的影响，导致这些细胞持续使用的几种细胞信号传导途径失调，以引发适当的免疫反应。有大量证据表明，气道上皮细胞、中性粒细胞、单核细胞和巨噬细胞均参与 CF 的发病机制，这表明 CFTR 在先天免疫反应中的重要性。本综述的目的是阐述 CFTR 在不同先天免疫细胞中的重要作用，以及 CFTR 功能障碍如何导致 CF 的发病机制，强调在 CFTR 突变的细胞中可能失调的几种信号通路。