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伴有鼻息肉的嗜酸性粒细胞性和非嗜酸性粒细胞性慢性鼻-鼻窦炎中的免疫细胞浸润及相关核心基因表达特征

Immune cell infiltration and related core genes expression characteristics in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps.

作者信息

Xiong Gaoyun, Xie Xiaoxing, Wang Qingliang, Zhang Yanyan, Ge Yanping, Lin Wei, Li Mingqian

机构信息

Department of Otolaryngology, Head and Neck Surgery, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China.

Cancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China.

出版信息

Exp Ther Med. 2020 Dec;20(6):180. doi: 10.3892/etm.2020.9310. Epub 2020 Oct 12.

Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) refers to chronic inflammation of the sinonasal mucosa. It can either be eosinophilic (ECRSwNP) or non-eosinophilic (non-ECRSwNP). However, immune cell infiltration in the microenvironment and pathogenesis of ECRSwNP and non-ECRSwNP are still unclear. The aim of the present study was to assess the immune cell infiltration and molecular mechanisms of ECRSwNP and non-ECRSwNP. In the present study, 22 immune cell types in ECRSwNP and non-ECRSwNP were investigated by CIBERSORT based on transcriptome data. The core gene related pathophysiology of CRSwNP was analyzed using Weighted Gene Correlation Network Analysis according to the phenotype of the infiltrated eosinophils and nasal polyps (NP). A total of four types of immune cells (mast cells, activated dendritic cells, M2 macrophages and activated natural killer cells) were demonstrated to have a direct and indirect correlation with eosinophilic infiltration in ECRSwNP. M1 macrophages and activated CD4 memory T cells were correlated with major immune cell types in non-ECRSwNP. NP could affect the expression of 'olfactory receptor activity' and 'channel activity' genes to impair the olfactory signaling pathway and neuroactive ligand receptor pathway. 'Cell adhesion molecule binding', 'cytokine receptor binding' and 'glucocorticoid receptor binding' were significantly enriched in ECRSwNP, whereas epithelial cell injury, autophagy and the mTOR pathway (hsa04140 and hsa04150) may serve an important role in the pathogenesis of non-ECRSwNP. There were significantly different immune cell infiltration and related core genes expression characteristics between ECRSwNP and non-ECRSwNP. The results of the present study provide an improved basis for elucidation of the mechanism and treatment of CRSwNP.

摘要

伴鼻息肉的慢性鼻-鼻窦炎(CRSwNP)是指鼻窦黏膜的慢性炎症。它可以是嗜酸性粒细胞性的(ECRSwNP)或非嗜酸性粒细胞性的(非ECRSwNP)。然而,ECRSwNP和非ECRSwNP微环境中的免疫细胞浸润及发病机制仍不清楚。本研究的目的是评估ECRSwNP和非ECRSwNP的免疫细胞浸润及分子机制。在本研究中,基于转录组数据,通过CIBERSORT对ECRSwNP和非ECRSwNP中的22种免疫细胞类型进行了研究。根据浸润嗜酸性粒细胞和鼻息肉(NP)的表型,使用加权基因共表达网络分析来分析CRSwNP相关病理生理学的核心基因。共证实四种免疫细胞类型(肥大细胞、活化树突状细胞、M2巨噬细胞和活化自然杀伤细胞)与ECRSwNP中的嗜酸性粒细胞浸润存在直接和间接关联。M1巨噬细胞和活化的CD4记忆T细胞与非ECRSwNP中的主要免疫细胞类型相关。NP可影响“嗅觉受体活性”和“通道活性”基因的表达,从而损害嗅觉信号通路和神经活性配体受体通路。“细胞黏附分子结合”、“细胞因子受体结合”和“糖皮质激素受体结合”在ECRSwNP中显著富集,而上皮细胞损伤、自噬和mTOR通路(hsa04140和hsa04150)可能在非ECRSwNP的发病机制中起重要作用。ECRSwNP和非ECRSwNP之间存在明显不同的免疫细胞浸润及相关核心基因表达特征。本研究结果为阐明CRSwNP的机制和治疗提供了更好的依据。

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