背景:慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)导致鼻塞和嗅觉功能障碍。阿司匹林加剧的呼吸系统疾病(AERD)是CRSwNP的三联症,哮喘和对环氧合酶-1抑制剂的呼吸反应。AERD患者的鼻腔IL-5水平升高,抗体分泌细胞(ASCs)数量高,浆细胞(PC)和成浆细胞,在他们的息肉组织中,鼻息肉IgE水平与疾病严重程度和鼻息肉病复发相关。
目的:我们试图探索转录组特征的差异,激活标记,AERD和CRSwNP患者鼻息肉ASCs的IL-5Rα表达和功能。
方法:从患有AERD和CRSwNP的患者收集鼻息肉组织并消化成单细胞悬液。通过质量细胞术分析鼻息肉细胞的蛋白质表达。对于IL-5Rα功能研究,纯化浆细胞并在有/无IL-5的情况下体外培养,并通过批量RNA测序进行分析。
结果:与CRSwNP相比,AERD息肉组织含有明显更多的ASCs,并且IL-5Rα的ASC表达增加。AERDASCs表达较高的B细胞活化和调节标记(CD40,CD19,CD32和CD38)和增殖标记Ki-67蛋白水平。AERDASCs也表达更多的IL5RA,IGHE,以及与CRSwNP相比的细胞周期和增殖相关转录物(CCND2、MKI67、CDC25A和CDC25B)。用IL-5诱导的关键细胞周期基因(CCND2和PTP4A3)刺激AERDPCs,而IL-5刺激来自CRSwNP的ASCs几乎不诱导转录组变化。
结论:与阿司匹林耐受CRSwNP患者相比,AERD患者的鼻息肉组织ASCs表达更高水平的功能性IL-5Rα和与细胞周期和增殖相关的标志物。
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) causes nasal obstruction and olfactory dysfunction. Aspirin-exacerbated respiratory disease (AERD) is the triad of CRSwNP, asthma, and respiratory reactions to COX-1 inhibitors. Patients with AERD have elevated nasal IL-5 levels and high numbers of antibody-secreting cells (ASCs), including plasma cells and plasmablasts, in their polyp tissue; in addition, their nasal polyp (NP) IgE levels are correlated with disease severity and recurrence of nasal polyposis.
OBJECTIVE: We sought to explore differences in the transcriptomic profile, activation markers, and IL-5Rα expression and function of NP ASCs from patients with AERD and CRSwNP.
METHODS: NP tissue was collected from patients with AERD and CRSwNP and digested into single-cell suspensions. NP cells were analyzed for protein expression by mass cytometry. For IL-5Rα functional studies, plasma cells were purified and cultured in vitro with or without IL-5 and analyzed by bulk RNA sequencing.
RESULTS: Compared with polyp tissue from patients with CRSwNP, polyp tissue from patients with AERD contained significantly more ASCs and had increased ASC expression of IL-5Rα. ASCs from patients with AERD expressed higher protein levels of B-cell activation and regulatory markers (CD40, CD19, CD32, and CD38) and the proliferation marker Ki-67. ASCs from patients with AERD also expressed more IL5RA, IGHE, and cell cycle- and proliferation-related transcripts (CCND2, MKI67, CDC25A, and CDC25B) than did ASCs from patients with CRSwNP. Stimulation of plasma cells from patients with AERD with IL-5 induced key cell cycle genes (CCND2 and PTP4A3), whereas IL-5 stimulation of ASCs from patients with CRSwNP induced few transcriptomic changes.
CONCLUSIONS: NP tissue ASCs from patients with AERD express higher levels of functional IL-5Rα and markers associated with cell cycling and proliferation than do ASCs from patients with aspirin-tolerant CRSwNP.