Impact of the cytokine milieu on fibroblasts and their characterization in chronic rhinosinusitis with nasal polyps.

IF 1 4区 医学 Q3 OTORHINOLARYNGOLOGY
Toshiyuki Matsuyama, Reika Kawabata-Iwakawa, Hideyuki Takahashi, Yuichi Tomidokoro, Masaomi Motegi, Kazuaki Chikamatsu
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引用次数: 0

Abstract

Background: Nasal polyps (NP) contribute to treatment resistance in chronic rhinosinusitis with nasal polyps (CRSwNP); however, the cellular and molecular mechanisms underlying nasal polypogenesis are not completely understood.

Objectives: To investigate whether the characteristics of fibroblasts differ under the surrounding tissue environment.

Material and methods: Patients with CRSwNP were divided into two groups based on the eosinophil infiltration in the NP; the gene expression levels were evaluated. Fibroblasts established from NP were assessed for functional changes following cytokine stimulation, and RNA sequencing (RNA-seq) was performed.

Results: IL5 and IL13 expression was higher, and IFNG and TNF lower, in NP from eosinophilic CRS (ECRS) patients compared to non-ECRS. FOXP3 expression was significantly upregulated in ECRS patients. Cytokine-stimulated fibroblasts from both ECRS and non-ECRS showed similar expression of fibroblast-to-myofibroblast transition-related genes and significantly reduced migratory capacity following IL-13 and TNF-α treatment. RNA sequencing revealed six and thirty-five significant activated and inactivated signaling pathways, respectively, in the Diseases Bio Functions analysis.

Conclusions and significance: Fibroblasts contribute to nasal polypogenesis irrespective of inflammation type in CRSwNP. Although their behavior is regulated by the immune microenvironment, our findings also highlight fibroblasts as potential therapeutic targets, supporting both endotypic classification and novel treatment strategies.

细胞因子环境对慢性鼻窦炎伴鼻息肉成纤维细胞的影响及其特征。
背景:鼻息肉(NP)是慢性鼻窦炎伴鼻息肉(CRSwNP)治疗耐药的因素之一;然而,鼻腔息肉形成的细胞和分子机制尚不完全清楚。目的:探讨成纤维细胞在周围组织环境下的特性差异。材料与方法:根据NP中嗜酸性粒细胞的浸润情况将CRSwNP患者分为两组;评估基因表达水平。在细胞因子刺激后,评估从NP中建立的成纤维细胞的功能变化,并进行RNA测序(RNA-seq)。结果:与非ECRS相比,嗜酸性CRS (ECRS)患者NP中IL5和IL13的表达较高,IFNG和TNF的表达较低。在ECRS患者中FOXP3表达显著上调。细胞因子刺激的ECRS和非ECRS成纤维细胞在IL-13和TNF-α处理后显示成纤维细胞向肌成纤维细胞过渡相关基因的表达相似,迁移能力显著降低。RNA测序在疾病生物功能分析中分别揭示了6个和35个重要的激活和失活信号通路。结论和意义:在CRSwNP中,无论炎症类型如何,成纤维细胞都有助于鼻息肉形成。尽管它们的行为受到免疫微环境的调节,但我们的研究结果也强调了成纤维细胞作为潜在的治疗靶点,支持内源性分类和新的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Acta Oto-Laryngologica
Acta Oto-Laryngologica 医学-耳鼻喉科学
CiteScore
2.50
自引率
0.00%
发文量
99
审稿时长
3-6 weeks
期刊介绍: Acta Oto-Laryngologica is a truly international journal for translational otolaryngology and head- and neck surgery. The journal presents cutting-edge papers on clinical practice, clinical research and basic sciences. Acta also bridges the gap between clinical and basic research.
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