Department of Ophthalmology and Visual Sciences, Case Western Reserve University, United States.
Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, United States.
Clin Immunol. 2016 Sep;170:53-60. doi: 10.1016/j.clim.2016.03.016. Epub 2016 May 4.
Cystic fibrosis (CF) is a chronic pulmonary disease that is associated with persistent microbial infection and chronic neutrophil infiltration, and also with elevated production of the pro-inflammatory cytokine IL-17A (IL-17). In the current study, we examined IL-17 and the inducible IL-17RC receptor subunit in neutrophils from Pseudomonas aeruginosa infected F508del CF patients at the time of pulmonary exacerbation, and again following intravenous antibiotic treatment. Neutrophils expressed Il17a and Il17rc transcripts and protein at the time of pulmonary exacerbation, which were absent following antibiotic treatment. Further, CF sputum induced IL-23 - dependent Il17rc expression in neutrophils from healthy individuals. Similarly, IL-17 producing neutrophils were detected in F508del and Cftr(-/-) mice infected intranasally with P. aeruginosa. In the sputum of CF subjects, the percentage IL-17 producing neutrophils correlated with elastase and MMP9 activity; therefore, this population of neutrophils may be an important contributor to the severity of pulmonary disease in CF patients.
囊性纤维化（CF）是一种慢性肺部疾病，与持续的微生物感染和慢性中性粒细胞浸润有关，同时还伴有促炎细胞因子 IL-17A（IL-17）的产生增加。在本研究中，我们在肺部恶化时检查了铜绿假单胞菌感染的 F508del CF 患者中性粒细胞中的 IL-17 和诱导型 IL-17RC 受体亚基，并在静脉用抗生素治疗后再次检查。中性粒细胞在肺部恶化时表达 Il17a 和 Il17rc 转录本和蛋白，而在抗生素治疗后则不存在。此外，CF 痰液可诱导健康个体中性粒细胞中 IL-23 依赖性 Il17rc 表达。同样，在经鼻感染铜绿假单胞菌的 F508del 和 Cftr(-/-) 小鼠中也检测到产生 IL-17 的中性粒细胞。在 CF 患者的痰液中，产生 IL-17 的中性粒细胞百分比与弹性蛋白酶和 MMP9 活性相关；因此，这群中性粒细胞可能是 CF 患者肺部疾病严重程度的重要贡献者。
