Department of Otolaryngology, The Second Hospital of Shandong University, Shandong University, No.274 Beiyuan Road, Jinan, 250033, Shandong Province, China.
Department of Otolaryngology, The Central Hospital of Zibo, No.54, Gongqingtuan West Road, Zhangdian District, Zibo, Shandong Province, China.
Inflammation. 2019 Feb;42(1):135-144. doi: 10.1007/s10753-018-0879-3.
The maturation of dendritic cells is critical for chronic rhinosinusitis with nasal polyps (CRSwNPs), especially eosinophilic chronic rhinosinusitis with nasal polyps (EosCRSwNPs), but the regulation mechanism of dendritic cells (DCs) maturation is still unclear. We identified nasal mucosa of 20 patients with EosCRSwNP, 16 non-EosCRSwNP patients, and inferior turbinate of 14 patients with nasal septum deviation after surgery. The expression of cyclin-dependent kinase 5 (CDK5) and programmed cell death 1 ligand 1 (PD-L1) were detected by immunofluorescent, real-time quantitative PCR, and Western blot in EosCRSwNP. The level of dendritic cell maturation was detected by flow cytometry and immunofluorescence staining after CDK5 expression interference with small interfering RNA (siRNA). The expression of CDK5 and PD-L1 in EosCRSwNP nasal mucosal tissue was significantly higher than that of non-EosCRSwNP and inferior turbinate nasal mucosa tissue, and there was a positive correlation between them. Immunofluorescence staining showed that CDK5 and PD-L1 were co-localized in dendritic cells. Synergistic stimulation of dendritic cells with LPS and TNF-α promotes the maturation of dendritic cells and increases the expression of CDK5 and PD-L1. However, blocking the expression of CDK5 in dendritic cells with siRNAs leads to a blockage of cell maturation. CDK5 can regulate the expression of PD-L1, and its presence is critical for the maturation of dendritic cells. CDK5 may play an important role in the pathogenesis of CRSwNP disease.
树突状细胞的成熟对于慢性鼻-鼻窦炎伴鼻息肉（CRSwNPs），尤其是嗜酸性粒细胞性慢性鼻-鼻窦炎伴鼻息肉（EosCRSwNPs）至关重要，但树突状细胞（DC）成熟的调控机制尚不清楚。我们鉴定了 20 例 EosCRSwNP 患者、16 例非 EosCRSwNP 患者和 14 例鼻中隔偏曲手术后患者的下鼻甲鼻黏膜组织。通过免疫荧光、实时定量 PCR 和 Western blot 检测 EosCRSwNP 中细胞周期蛋白依赖性激酶 5（CDK5）和程序性细胞死亡配体 1（PD-L1）的表达。用小干扰 RNA（siRNA）干扰 CDK5 表达后，通过流式细胞术和免疫荧光染色检测树突状细胞成熟水平。EosCRSwNP 鼻黏膜组织中 CDK5 和 PD-L1 的表达明显高于非 EosCRSwNP 和下鼻甲鼻黏膜组织，且二者呈正相关。免疫荧光染色显示，CDK5 和 PD-L1 在树突状细胞中存在共定位。LPS 和 TNF-α 协同刺激树突状细胞可促进树突状细胞成熟，并增加 CDK5 和 PD-L1 的表达。然而，用 siRNAs 阻断树突状细胞中 CDK5 的表达会导致细胞成熟受阻。CDK5 可以调节 PD-L1 的表达，其存在对于树突状细胞的成熟至关重要。CDK5 可能在 CRSwNP 疾病的发病机制中发挥重要作用。
